Adipose tissue dysfunction and its effects on tumor metabolism

References

1. Sethi JK, Vidal-Puig AJ. Thematic review series: adipocyte biology. Adipose tissue function and plasticity orchestrate nutritional adaptation. J Lipid Res 2007;48:1253–62.10.1194/jlr.R700005-JLR200Suche in Google Scholar PubMed PubMed Central

2. Frayn KN, Karpe F, Fielding BA, Macdonald IA, Coppack SW. Integrative physiology of human adipose tissue. Int J Obes Relat Metab Disord 2003;27:875–88.10.1038/sj.ijo.0802326Suche in Google Scholar PubMed

3. Lean ME. Brown adipose tissue in humans. Proc Nutr Soc 1989;48:243–56.10.1079/PNS19890036Suche in Google Scholar

4. Timmons JA, Wennmalm K, Larsson O, Walden TB, Lassmann T, Petrovic N, Hamilton DL, Gimeno RE, Wahlestedt C, Baar K, Nedergaard J, Cannon B. Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineages. Proc Natl Acad Sci USA 2007;104:4401–6.10.1073/pnas.0610615104Suche in Google Scholar PubMed PubMed Central

5. Heaton JM. The distribution of brown adipose tissue in the human. J Anat 1972;112(Pt 1):35–9.Suche in Google Scholar

6. Cypess AM, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, Kuo FC, Palmer EL, Tseng YH, Doria A, Kolodny GM, Kahn CR. Identification and importance of brown adipose tissue in adult humans. N Engl J Med 2009;360:1509–17.10.1056/NEJMoa0810780Suche in Google Scholar PubMed PubMed Central

7. van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, Drossaerts JM, Kemerink GJ, Bouvy ND, Schrauwen P, Teule GJ. Cold-activated brown adipose tissue in healthy men. N Engl J Med 2009;360:1500–8.10.1056/NEJMoa0808718Suche in Google Scholar PubMed

8. Ouellet V, Labbe SM, Blondin DP, Phoenix S, Guerin B, Haman F, Turcotte EE, Richard D, Carpentier AC. Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans. J Clin Invest 2012;122:545–52.10.1172/JCI60433Suche in Google Scholar PubMed PubMed Central

9. Melicow MM. Hibernating fat and pheochromocytoma. AMA Arch Pathol 1957;63:367–72.Suche in Google Scholar

10. Soderlund V, Larsson SA, Jacobsson H. Reduction of FDG uptake in brown adipose tissue in clinical patients by a single dose of propranolol. Eur J Nucl Med Mol Imaging 2007;34:1018–22.10.1007/s00259-006-0318-9Suche in Google Scholar PubMed

11. Lee P, Swarbrick MM, Ho KK. Brown adipose tissue in adult humans: a metabolic renaissance. Endocrine Rev 2013;34: 413–38.10.1210/er.2012-1081Suche in Google Scholar PubMed

12. Guerra C, Koza RA, Yamashita H, Walsh K, Kozak LP. Emergence of brown adipocytes in white fat in mice is under genetic control. Effects on body weight and adiposity. J Clin Invest 1998;102:412–20.10.1172/JCI3155Suche in Google Scholar PubMed PubMed Central

13. Vijgen GH, Bouvy ND, Teule GJ, Brans B, Hoeks J, Schrauwen P, van Marken Lichtenbelt WD. Increase in brown adipose tissue activity after weight loss in morbidly obese subjects. J Clin Endocrinol Metab 2012;97:1229–33.10.1210/jc.2012-1289Suche in Google Scholar PubMed

14. Giralt M, Villarroya F. White, brown, beige/brite: different adipose cells for different functions? Endocrinology 2013;154:2992–3000.10.1210/en.2013-1403Suche in Google Scholar PubMed

15. Lee YH, Mottillo EP, Granneman JG. Adipose tissue plasticity from WAT to BAT and in between. Biochim Biophys Acta 2014;1842:358–69.10.1016/j.bbadis.2013.05.011Suche in Google Scholar PubMed PubMed Central

16. Harrington TA, Thomas EL, Frost G, Modi N, Bell JD. Distribution of adipose tissue in the newborn. Pediatr Res 2004;55:437–41.10.1203/01.PDR.0000111202.29433.2DSuche in Google Scholar PubMed

17. Hamdy O, Porramatikul S, Al-Ozairi E. Metabolic obesity: the paradox between visceral and subcutaneous fat. Curr Diabetes Rev 2006;2:367–73.10.2174/1573399810602040367Suche in Google Scholar PubMed

18. Nishino N, Tamori Y, Tateya S, Kawaguchi T, Shibakusa T, Mizunoya W, Inoue K, Kitazawa R, Kitazawa S, Matsuki Y, Hiramatsu R, Masubuchi S, Omachi A, Kimura K, Saito M, Amo T, Ohta S, Yamaguchi T, Osumi T, Cheng J, Fujimoto T, Nakao H, Nakao K, Aiba A, Okamura H, Fushiki T, Kasuga M. FSP27 contributes to efficient energy storage in murine white adipocytes by promoting the formation of unilocular lipid droplets. J Clin Invest 2008;118:2808–21.10.1172/JCI34090Suche in Google Scholar PubMed PubMed Central

19. Harms M, Seale P. Brown and beige fat: development, function and therapeutic potential. Nat Med 2013;19:1252–63.10.1038/nm.3361Suche in Google Scholar PubMed

20. Cousin B, Cinti S, Morroni M, Raimbault S, Ricquier D, Penicaud L, Casteilla L. Occurrence of brown adipocytes in rat white adipose tissue: molecular and morphological characterization. J Cell Sci 1992;103(Pt 4):931–42.10.1242/jcs.103.4.931Suche in Google Scholar PubMed

21. Granneman JG, Li P, Zhu Z, Lu Y. Metabolic and cellular plasticity in white adipose tissue I: effects of beta3-adrenergic receptor activation. Am J Physiol 2005;289:E608–16.10.1152/ajpendo.00009.2005Suche in Google Scholar PubMed

22. Himms-Hagen J, Cui J, Danforth E Jr., Taatjes DJ, Lang SS, Waters BL, Claus TH. Effect of CL-316,243, a thermogenic beta 3-agonist, on energy balance and brown and white adipose tissues in rats. Am J Physiol 1994;266:R1371–82.10.1152/ajpregu.1994.266.4.R1371Suche in Google Scholar PubMed

23. Seale P, Bjork B, Yang W, Kajimura S, Chin S, Kuang S, Scime A, Devarakonda S, Conroe HM, Erdjument-Bromage H, Tempst P, Rudnicki MA, Beier DR, Spiegelman BM. PRDM16 controls a brown fat/skeletal muscle switch. Nature 2008;454:961–7.10.1038/nature07182Suche in Google Scholar PubMed PubMed Central

24. Hardaway AL, Herroon MK, Rajagurubandara E, Podgorski I. Bone marrow fat: linking adipocyte-induced inflammation with skeletal metastases. Cancer Metastasis Rev 2014;33:527–43.10.1007/s10555-013-9484-ySuche in Google Scholar PubMed PubMed Central

25. Lecka-Czernik B. Marrow fat metabolism is linked to the systemic energy metabolism. Bone 2011;50:534–9.10.1016/j.bone.2011.06.032Suche in Google Scholar PubMed PubMed Central

26. Lecka-Czernik B, Rosen CJ, Kawai M. Skeletal aging and the adipocyte program: New nsights from an “old” molecule. Cell Cycle 2010;9:3648–54.10.4161/cc.9.18.13046Suche in Google Scholar PubMed PubMed Central

27. Rosen CJ, Ackert-Bicknell C, Rodriguez JP, Pino AM. Marrow fat and the bone microenvironment: developmental, functional, and pathological implications. Crit Rev Eukaryot Gene Expr 2009;19:109–24.10.1615/CritRevEukarGeneExpr.v19.i2.20Suche in Google Scholar

28. Lecka-Czernik B. PPARs in bone: the role in bone cell differentiation and regulation of energy metabolism. Curr Osteoporos Rep 2010;8:84–90.10.1007/s11914-010-0016-1Suche in Google Scholar PubMed

29. Paula FJ, Rosen CJ. Obesity, diabetes mellitus and last but not least, osteoporosis. Arq Bras Endocrinol Metabol 2010;54:150–7.10.1590/S0004-27302010000200010Suche in Google Scholar PubMed

30. Lee NK, Sowa H, Hinoi E, Ferron M, Ahn JD, Confavreux C, Dacquin R, Mee PJ, McKee MD, Jung DY, Zhang Z, Kim JK, Mauvais-Jarvis F, Ducy P, Karsenty G. Endocrine regulation of energy metabolism by the skeleton. Cell 2007;130:456–69.10.1016/j.cell.2007.05.047Suche in Google Scholar PubMed PubMed Central

31. Cao JJ. Effects of obesity on bone metabolism. J Orthop Surg Res 2011;6:30.10.1186/1749-799X-6-30Suche in Google Scholar PubMed PubMed Central

32. Duque G. Bone and fat connection in aging bone. Curr Opin Rheumatol 2008;20:429–34.10.1097/BOR.0b013e3283025e9cSuche in Google Scholar PubMed

33. Villareal DT, Apovian CM, Kushner RF, Klein S, American Society for N, Naaso TOS. Obesity in older adults: technical review and position statement of the American Society for Nutrition and NAASO, The Obesity Society. Am J Clin Nutr 2005;82:923–34.10.1093/ajcn/82.5.923Suche in Google Scholar

34. Kugel H, Jung C, Schulte O, Heindel W. Age- and sex-specific differences in the 1H-spectrum of vertebral bone marrow. J Magn Reson Imaging 2001;13:263–8.10.1002/1522-2586(200102)13:2<263::AID-JMRI1038>3.0.CO;2-MSuche in Google Scholar

35. Nielson CM, Srikanth P, Orwoll ES. Obesity and fracture in men and women: an epidemiologic perspective. J Bone Miner Res 2012;27:1–10.10.1002/jbmr.1486Suche in Google Scholar

36. Owusu W, Willett W, Ascherio A, Spiegelman D, Rimm E, Feskanich D, Colditz G. Body anthropometry and the risk of hip and wrist fractures in men: results from a prospective study. Obesity Res 1998;6:12–9.10.1002/j.1550-8528.1998.tb00309.xSuche in Google Scholar

37. Cao JJ, Sun L, Gao H. Diet-induced obesity alters bone remodeling leading to decreased femoral trabecular bone mass in mice. Ann N Y Acad Sci 2010;1192:292–7.10.1111/j.1749-6632.2009.05252.xSuche in Google Scholar

38. Halade GV, Rahman MM, Williams PJ, Fernandes G. High fat diet-induced animal model of age-associated obesity and osteoporosis. J Nutr Biochem 2010;21:1162–9.10.1016/j.jnutbio.2009.10.002Suche in Google Scholar

39. Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 1988;37:1595–607.10.2337/diab.37.12.1595Suche in Google Scholar

40. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith Jr SC, Spertus JA, Costa F. Diagnosis and management of the metabolic syndrome. An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Executive summary. Cardiol Rev 2005;13:322–7.10.1097/01.crd.0000380842.14048.7eSuche in Google Scholar

41. Grundy SM, Cleeman JI, Merz CN, Brewer HB, Jr., Clark LT, Hunninghake DB, Pasternak RC, Smith SC Jr., Stone NJ. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines. J Am Coll Cardiol 2004;44:720–32.10.1016/j.jacc.2004.07.001Suche in Google Scholar

42. Ford ES, Abbasi F, Reaven GM. Prevalence of insulin resistance and the metabolic syndrome with alternative definitions of impaired fasting glucose. Atherosclerosis 2005;181:143–8.10.1016/j.atherosclerosis.2005.01.002Suche in Google Scholar

43. Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. J Am Med Assoc 2002;287:356–9.10.1001/jama.287.3.356Suche in Google Scholar

44. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, Smith SC Jr. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 2009;120:1640–5.10.1161/CIRCULATIONAHA.109.192644Suche in Google Scholar

45. Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet 2005;365:1415–28.10.1016/S0140-6736(05)66378-7Suche in Google Scholar

46. Goodpaster BH, Krishnaswami S, Resnick H, Kelley DE, Haggerty C, Harris TB, Schwartz AV, Kritchevsky S, Newman AB. Association between regional adipose tissue distribution and both type 2 diabetes and impaired glucose tolerance in elderly men and women. Diabetes Care 2003;26:372–9.10.2337/diacare.26.2.372Suche in Google Scholar

47. Mori Y, Hoshino K, Yokota K, Itoh Y, Tajima N. Differences in the pathology of the metabolic syndrome with or without visceral fat accumulation: a study in pre-diabetic Japanese middle-aged men. Endocrine 2006;29:149–53.10.1385/ENDO:29:1:149Suche in Google Scholar

48. Baum T, Yap SP, Karampinos DC, Nardo L, Kuo D, Burghardt AJ, Masharani UB, Schwartz AV, Li X, Link TM. Does vertebral bone marrow fat content correlate with abdominal adipose tissue, lumbar spine bone mineral density, and blood biomarkers in women with type 2 diabetes mellitus? J Magn Reson Imaging 2012;35:117–24.10.1002/jmri.22757Suche in Google Scholar PubMed PubMed Central

49. Sheu Y, Cauley JA. The role of bone marrow and visceral fat on bone metabolism. Curr Osteoporos Rep 2011;9:67–75.10.1007/s11914-011-0051-6Suche in Google Scholar PubMed PubMed Central

50. Botolin S, McCabe LR. Bone loss and increased bone adiposity in spontaneous and pharmacologically induced diabetic mice. Endocrinology 2007;148:198–205.10.1210/en.2006-1006Suche in Google Scholar PubMed

51. Schwartz AV, Sellmeyer DE. Diabetes, fracture, and bone fragility. Curr Osteoporos Rep 2007;5:105–11.10.1007/s11914-007-0025-xSuche in Google Scholar PubMed

52. Strotmeyer ES, Cauley JA. Diabetes mellitus, bone mineral density, and fracture risk. Curr Opin Endocrinol Diabetes Obes 2007;14:429–35.10.1097/MED.0b013e3282f1cba3Suche in Google Scholar PubMed

53. Isidro ML, Ruano B. Bone disease in diabetes. Curr Diabetes Rev 2010;6:144–55.10.2174/157339910791162970Suche in Google Scholar PubMed

54. Lee P, van der Wall H, Seibel MJ. Looking beyond low bone mineral density: multiple insufficiency fractures in a woman with post-menopausal osteoporosis on alendronate therapy. J Endocrinol Invest 2007;30:590–7.10.1007/BF03346353Suche in Google Scholar PubMed

55. Takizawa M, Suzuki K, Matsubayashi T, Kikuyama M, Suzuki H, Takahashi K, Katsuta H, Mitsuhashi J, Nishida S, Yamaguchi S, Yoshimoto K, Itagaki E, Ishida H. Increased bone resorption may play a crucial role in the occurrence of osteopenia in patients with type 2 diabetes: Possible involvement of accelerated polyol pathway in its pathogenesis. Diabetes Res Clin Pract 2008;82:119–26.10.1016/j.diabres.2008.07.008Suche in Google Scholar PubMed

56. Duarte VM, Ramos AM, Rezende LA, Macedo UB, Brandao-Neto J, Almeida MG, Rezende AA. Osteopenia: a bone disorder associated with diabetes mellitus. J Bone Miner Metab 2005;23:58–68.10.1007/s00774-004-0542-ySuche in Google Scholar PubMed

57. Hie M, Shimono M, Fujii K, Tsukamoto I. Increased cathepsin K and tartrate-resistant acid phosphatase expression in bone of streptozotocin-induced diabetic rats. Bone 2007;41:1045–50.10.1016/j.bone.2007.08.030Suche in Google Scholar PubMed

58. Pittas AG, Harris SS, Eliades M, Stark P, Dawson-Hughes B. Association between serum osteocalcin and markers of metabolic phenotype. J Clin Endocrinol Metab 2009;94:827–32.10.1210/jc.2008-1422Suche in Google Scholar PubMed PubMed Central

59. Saleem U, Mosley TH Jr., Kullo IJ. Serum osteocalcin is associated with measures of insulin resistance, adipokine levels, and the presence of metabolic syndrome. Arterioscler Thromb Vasc Biol 2010;30:1474–8.10.1161/ATVBAHA.110.204859Suche in Google Scholar PubMed PubMed Central

60. Gannage-Yared MH, Fares F, Semaan M, Khalife S, Jambart S. Circulating osteoprotegerin is correlated with lipid profile, insulin sensitivity, adiponectin and sex steroids in an ageing male population. Clin Endocrinol 2006;64:652–8.10.1111/j.1365-2265.2006.02522.xSuche in Google Scholar PubMed

61. Lazarenko OP, Rzonca SO, Hogue WR, Swain FL, Suva LJ, Lecka-Czernik B. Rosiglitazone induces decreases in bone mass and strength that are reminiscent of aged bone. Endocrinology 2007;148:2669–80.10.1210/en.2006-1587Suche in Google Scholar PubMed PubMed Central

62. Patsch JM, Li X, Baum T, Yap SP, Karampinos DC, Schwartz AV, Link TM. Bone marrow fat composition as a novel imaging biomarker in postmenopausal women with prevalent fragility fractures. J Bone Miner Res 2013;28:1721–8.10.1002/jbmr.1950Suche in Google Scholar PubMed PubMed Central

63. Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 2004;89:2548–56.10.1210/jc.2004-0395Suche in Google Scholar PubMed

64. Diez JJ, Iglesias P. The role of the novel adipocyte-derived hormone adiponectin in human disease. Eur J Endocrinol 2003;148:293–300.Suche in Google Scholar

65. Kadowaki T, Yamauchi T. Adiponectin and adiponectin receptors. Endocrine Rev 2005;26:439–51.10.1210/er.2005-0005Suche in Google Scholar PubMed

66. Hug C, Wang J, Ahmad NS, Bogan JS, Tsao TS, Lodish HF. T-cadherin is a receptor for hexameric and high-molecular-weight forms of Acrp30/adiponectin. Proc Natl Acad Sci USA 2004;101:10308–13.10.1073/pnas.0403382101Suche in Google Scholar PubMed PubMed Central

67. Tomas E, Tsao T-S, Saha AK, Murrey HE, Zhang Cc Cc, Itani SI, Lodish HF, Ruderman NB. Enhanced muscle fat oxidation and glucose transport by ACRP30 globular domain: acetyl-CoA carboxylase inhibition and AMP-activated protein kinase activation. Proc Natl Acad Sci USA 2002;99:16309–13.10.1073/pnas.222657499Suche in Google Scholar PubMed PubMed Central

68. Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S, Yamashita S, Noda M, Kita S, Ueki K, Eto K, Akanuma Y, Froguel P, Foufelle F, Ferre P, Carling D, Kimura S, Nagai R, Kahn BB, Kadowaki T. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med 2002;8:1288–95.10.1038/nm788Suche in Google Scholar PubMed

69. Yamauchi T, Kamon J, Waki H, Imai Y, Shimozawa N, Hioki K, Uchida S, Ito Y, Takakuwa K, Matsui J, Takata M, Eto K, Terauchi Y, Komeda K, Tsunoda M, Murakami K, Ohnishi Y, Naitoh T, Yamamura K, Ueyama Y, Froguel P, Kimura S, Nagai R, Kadowaki T. Globular adiponectin protected ob/ob mice from diabetes and ApoE-deficient mice from atherosclerosis. J Biol Chem 2003;278:2461–8.10.1074/jbc.M209033200Suche in Google Scholar PubMed

70. Liu M, Liu F. Up- and down-regulation of adiponectin expression and multimerization: mechanisms and therapeutic implication. Biochimie 2012;94:2126–30.10.1016/j.biochi.2012.01.008Suche in Google Scholar PubMed PubMed Central

71. Ryan AS, Berman DM, Nicklas BJ, Sinha M, Gingerich RL, Meneilly GS, Egan JM, Elahi D. Plasma adiponectin and leptin levels, body composition, and glucose utilization in adult women with wide ranges of age and obesity. Diabetes Care 2003;26:2383–8.10.2337/diacare.26.8.2383Suche in Google Scholar PubMed

72. Cawthorn WP, Scheller EL, Learman BS, Parlee SD, Simon BR, Mori H, Ning X, Bree AJ, Schell B, Broome DT, Soliman SS, DelProposto JL, Lumeng CN, Mitra A, Pandit SV, Gallagher KA, Miller JD, Krishnan V, Hui SK, Bredella MA, Fazeli PK, Klibanski A, Horowitz MC, Rosen CJ, MacDougald OA. Bone marrow adipose tissue is an endocrine organ that contributes to increased circulating adiponectin during caloric restriction. Cell Metab 2014;20:368–75.10.1016/j.cmet.2014.06.003Suche in Google Scholar PubMed PubMed Central

73. Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S, Sugiyama T, Miyagishi M, Hara K, Tsunoda M, Murakami K, Ohteki T, Uchida S, Takekawa S, Waki H, Tsuno NH, Shibata Y, Terauchi Y, Froguel P, Tobe K, Koyasu S, Taira K, Kitamura T, Shimizu T, Nagai R, Kadowaki T. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 2003;423:762–9.10.1038/nature01705Suche in Google Scholar PubMed

74. Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, Tataranni PA. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 2001;86:1930–5.10.1210/jcem.86.5.7463Suche in Google Scholar

75. Spranger J, Kroke A, Möhlig M, Bergmann MM, Ristow M, Boeing H, Pfeiffer AF. Adiponectin and protection against type 2 diabetes mellitus. Lancet 2003;361:226–8.10.1016/S0140-6736(03)12255-6Suche in Google Scholar

76. Iwashima Y, Katsuya T, Ishikawa K, Ouchi N, Ohishi M, Sugimoto K, Fu Y, Motone M, Yamamoto K, Matsuo A, Ohashi K, Kihara S, Funahashi T, Rakugi H, Matsuzawa Y, Ogihara T. Hypoadiponectinemia is an independent risk factor for hypertension. Hypertension 2004;43:1318–23.10.1161/01.HYP.0000129281.03801.4bSuche in Google Scholar PubMed

77. Williams KW, Scott MM, Elmquist JK. From observation to experimentation: leptin action in the mediobasal hypothalamus. Am J Clin Nutr 2009;89:985S–90S.10.3945/ajcn.2008.26788DSuche in Google Scholar PubMed PubMed Central

78. Schwartz MW, Woods SC, Porte D, Seeley RJ, Baskin DG. Central nervous system control of food intake. Nature 2000;404:661–71.10.1038/35007534Suche in Google Scholar PubMed

79. Myers MG. Leptin receptor signaling and the regulation of mammalian physiology. Recent Prog Horm Res 2004;59:287–304.10.1210/rp.59.1.287Suche in Google Scholar PubMed

80. Clement K, Vaisse C, Lahlou N, Cabrol S, Pelloux V, Cassuto D, Gourmelen M, Dina C, Chambaz J, Lacorte JM, Basdevant A, Bougneres P, Lebouc Y, Froguel P, Guy-Grand B. A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature 1998;392:398–401.10.1038/32911Suche in Google Scholar PubMed

81. Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, Ohannesian JP, Marco CC, McKee LJ, Bauer TL, Caro JF. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. New Engl J Med 1996;334: 292–5.10.1056/NEJM199602013340503Suche in Google Scholar PubMed

82. Garofalo C, Surmacz E. Leptin and cancer. J Cell Physiol 2006;207:12–22.10.1002/jcp.20472Suche in Google Scholar PubMed

83. Zheng Q, Banaszak L, Fracci S, Basali D, Dunlap SM, Hursting SD, Rich JN, Hjlemeland AB, Vasanji A, Berger NA, Lathia JD, Reizes O. Leptin receptor maintains cancer stem-like properties in triple negative breast cancer cells. Endocr Relat Cancer 2013;20:797–808.10.1530/ERC-13-0329Suche in Google Scholar PubMed PubMed Central

84. Neels JG, Olefsky JM. Inflamed fat: what starts the fire? J Clin Invest 2006;116:33–5.10.1172/JCI27280Suche in Google Scholar PubMed PubMed Central

85. Cancello R, Henegar C, Viguerie N, Taleb S, Poitou C, Rouault C, Coupaye M, Pelloux V, Hugol D, Bouillot JL, Bouloumie A, Barbatelli G, Cinti S, Svensson PA, Barsh GS, Zucker JD, Basdevant A, Langin D, Clement K. Reduction of macrophage infiltration and chemoattractant gene expression changes in white adipose tissue of morbidly obese subjects after surgery-induced weight loss. Diabetes 2005;54:2277–86.10.2337/diabetes.54.8.2277Suche in Google Scholar PubMed

86. Sun S, Ji Y, Kersten S, Qi L. Mechanisms of inflammatory responses in obese adipose tissue. Annu Rev Nutr 2012;32:261–86.10.1146/annurev-nutr-071811-150623Suche in Google Scholar PubMed PubMed Central

87. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 2003;112:1796–808.10.1172/JCI200319246Suche in Google Scholar

88. Makki K, Froguel P, Wolowczuk I. Adipose tissue in obesity-related inflammation and insulin resistance: cells, cytokines, and chemokines. ISRN Inflamm 2013:139239. doi: 10.1155/2013/139239.10.1155/2013/139239Suche in Google Scholar PubMed PubMed Central

89. Nguyen MT, Satoh H, Favelyukis S, Babendure JL, Imamura T, Sbodio JI, Zalevsky J, Dahiyat BI, Chi NW, Olefsky JM. JNK and tumor necrosis factor-alpha mediate free fatty acid-induced insulin resistance in 3T3-L1 adipocytes. J Biol Chem 2005;280:35361–71.10.1074/jbc.M504611200Suche in Google Scholar PubMed

90. Souza SC, Palmer HJ, Kang YH, Yamamoto MT, Muliro KV, Paulson KE, Greenberg AS. TNF-alpha induction of lipolysis is mediated through activation of the extracellular signal related kinase pathway in 3T3-L1 adipocytes. J Cell Biochem 2003;89:1077–86.10.1002/jcb.10565Suche in Google Scholar PubMed

91. Hivert MF, Sullivan LM, Fox CS, Nathan DM, D’Agostino RB Sr, Wilson PW, Meigs JB. Associations of adiponectin, resistin, and tumor necrosis factor-alpha with insulin resistance. J Clin Endocrinol Metab 2008;93:3165–72.10.1210/jc.2008-0425Suche in Google Scholar PubMed PubMed Central

92. Park EJ, Lee JH, Yu GY, He G, Ali SR, Holzer RG, Osterreicher CH, Takahashi H, Karin M. Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL-6 and TNF expression. Cell 2010;140:197–208.10.1016/j.cell.2009.12.052Suche in Google Scholar PubMed PubMed Central

93. Wang B, Wood IS, Trayhurn P. Dysregulation of the expression and secretion of inflammation-related adipokines by hypoxia in human adipocytes. Pflugers Archiv 2007;455:479–92.10.1007/s00424-007-0301-8Suche in Google Scholar PubMed PubMed Central

94. Kern PA, Ranganathan S, Li C, Wood L, Ranganathan G. Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. Am J Physiol 2001;280:E745–51.10.1152/ajpendo.2001.280.5.E745Suche in Google Scholar

95. Yadav A, Kumar B, Datta J, Teknos TN, Kumar P. IL-6 promotes head and neck tumor metastasis by inducing epithelial-mesenchymal transition via the JAK-STAT3-SNAIL signaling pathway. Mol Cancer Res 2011;9:1658–67.10.1158/1541-7786.MCR-11-0271Suche in Google Scholar

96. Lagathu C, Yvan-Charvet L, Bastard JP, Maachi M, Quignard-Boulange A, Capeau J, Caron M. Long-term treatment with interleukin-1beta induces insulin resistance in murine and human adipocytes. Diabetologia 2006;49:2162–73.10.1007/s00125-006-0335-zSuche in Google Scholar

97. Larsen CM, Faulenbach M, Vaag A, Volund A, Ehses JA, Seifert B, Mandrup-Poulsen T, Donath MY. Interleukin-1-receptor antagonist in type 2 diabetes mellitus. N Engl J Med 2007;356:1517–26.10.1056/NEJMoa065213Suche in Google Scholar

98. Martin S, Parton RG. Lipid droplets: a unified view of a dynamic organelle. Nat Rev Mol Cell Biol 2006;7:373–8.10.1038/nrm1912Suche in Google Scholar

99. Rajala MW, Scherer PE. Minireview: The adipocyte–at the crossroads of energy homeostasis, inflammation, and atherosclerosis. Endocrinology 2003;144:3765–73.10.1210/en.2003-0580Suche in Google Scholar

100. Langin D. Adipose tissue lipolysis as a metabolic pathway to define pharmacological strategies against obesity and the metabolic syndrome. Pharmacol Res 2006;53:482–91.10.1016/j.phrs.2006.03.009Suche in Google Scholar

101. Lafontan M, Berlan M. Characterization of physiological agonist selectivity of human fat cell alpha 2-adrenoceptors: adrenaline is the major stimulant of the alpha 2-adrenoceptors. Eur J Pharmacol 1982;82:107–11.10.1016/0014-2999(82)90562-3Suche in Google Scholar

102. Honnor RC, Dhillon GS, Londos C. cAMP-dependent protein kinase and lipolysis in rat adipocytes. I. Cell preparation, manipulation, and predictability in behavior. J Biol Chem 1985;260:15122–9.10.1016/S0021-9258(18)95711-XSuche in Google Scholar

103. Honnor RC, Dhillon GS, Londos C. cAMP-dependent protein kinase and lipolysis in rat adipocytes. II. Definition of steady-state relationship with lipolytic and antilipolytic modulators. J Biol Chem 1985;260:15130–8.10.1016/S0021-9258(18)95712-1Suche in Google Scholar

104. Greenberg AS, Egan JJ, Wek SA, Garty NB, Blanchette-Mackie EJ, Londos C. Perilipin, a major hormonally regulated adipocyte-specific phosphoprotein associated with the periphery of lipid storage droplets. J Biol Chem 1991;266:11341–6.10.1016/S0021-9258(18)99168-4Suche in Google Scholar

105. Zimmermann R, Strauss JG, Haemmerle G, Schoiswohl G, Birner-Gruenberger R, Riederer M, Lass A, Neuberger G, Eisenhaber F, Hermetter A, Zechner R. Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase. Science 2004;306:1383–6.10.1126/science.1100747Suche in Google Scholar PubMed

106. Haemmerle G, Zimmermann R, Hayn M, Theussl C, Waeg G, Wagner E, Sattler W, Magin TM, Wagner EF, Zechner R. Hormone-sensitive lipase deficiency in mice causes diglyceride accumulation in adipose tissue, muscle, and testis. J Biol Chem 2002;277:4806–15.10.1074/jbc.M110355200Suche in Google Scholar PubMed

107. Haemmerle G, Lass A, Zimmermann R, Gorkiewicz G, Meyer C, Rozman J, Heldmaier G, Maier R, Theussl C, Eder S, Kratky D, Wagner EF, Klingenspor M, Hoefler G, Zechner R. Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase. Science 2006;312:734–7.10.1126/science.1123965Suche in Google Scholar PubMed

108. Kershaw EE, Hamm JK, Verhagen LA, Peroni O, Katic M, Flier JS. Adipose triglyceride lipase: function, regulation by insulin, and comparison with adiponutrin. Diabetes 2006;55:148–57.10.2337/diabetes.55.01.06.db05-0982Suche in Google Scholar

109. Miyoshi H, Perfield JW, Souza SC, Shen W-J, Zhang H-H, Stancheva ZS, Kraemer FB, Obin MS, Greenberg AS. Control of adipose triglyceride lipase action by serine 517 of perilipin A globally regulates protein kinase A-stimulated lipolysis in adipocytes. J Biol Chem 2007;282:996–1002.10.1074/jbc.M605770200Suche in Google Scholar PubMed

110. Akiyama M, Sakai K, Ogawa M, McMillan JR, Sawamura D, Shimizu H. Novel duplication mutation in the patatin domain of adipose triglyceride lipase (PNPLA2) in neutral lipid storage disease with severe myopathy. Muscle Nerve 2007;36:856–9.10.1002/mus.20869Suche in Google Scholar PubMed

111. Fischer J, Lefèvre C, Morava E, Mussini J-M, Laforêt P, Negre-Salvayre A, Lathrop M, Salvayre R. The gene encoding adipose triglyceride lipase (PNPLA2) is mutated in neutral lipid storage disease with myopathy. Nat Genet 2007;39:28–30.10.1038/ng1951Suche in Google Scholar PubMed

112. Kobayashi K, Inoguchi T, Maeda Y, Nakashima N, Kuwano A, Eto E, Ueno N, Sasaki S, Sawada F, Fujii M, Matoba Y, Sumiyoshi S, Kawate H, Takayanagi R. The lack of the C-terminal domain of adipose triglyceride lipase causes neutral lipid storage disease through impaired interactions with lipid droplets. J Clin Endocrinol Metab 2008;93:2877–84.10.1210/jc.2007-2247Suche in Google Scholar PubMed

113. Zechner R, Kienesberger PC, Haemmerle G, Zimmermann R, Lass A. Adipose triglyceride lipase and the lipolytic catabolism of cellular fat stores. J Lipid Res 2009;50:3–21.10.1194/jlr.R800031-JLR200Suche in Google Scholar PubMed

114. Schiffelers SL, Saris WH, Boomsma F, van Baak MA. beta(1)- and beta(2)-Adrenoceptor-mediated thermogenesis and lipid utilization in obese and lean men. J Clin Endocrinol Metab 2001;86:2191–9.Suche in Google Scholar

115. Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of childhood and adult obesity in the United States, 2011–2012. J Am Med Assoc 2014;311:806–14.10.1001/jama.2014.732Suche in Google Scholar

116. Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, Mullany EC, Biryukov S, Abbafati C, Abera SF, Abraham JP, Abu-Rmeileh NM, Achoki T, AlBuhairan FS, Alemu ZA, Alfonso R, Ali MK, Ali R, Guzman NA, Ammar W, Anwari P, Banerjee A, Barquera S, Basu S, Bennett DA, Bhutta Z, Blore J, Cabral N, Nonato IC, Chang JC, Chowdhury R, Courville KJ, Criqui MH, Cundiff DK, Dabhadkar KC, Dandona L, Davis A, Dayama A, Dharmaratne SD, Ding EL, Durrani AM, Esteghamati A, Farzadfar F, Fay DF, Feigin VL, Flaxman A, Forouzanfar MH, Goto A, Green MA, Gupta R, Hafezi-Nejad N, Hankey GJ, Harewood HC, Havmoeller R, Hay S, Hernandez L, Husseini A, Idrisov BT, Ikeda N, Islami F, Jahangir E, Jassal SK, Jee SH, Jeffreys M, Jonas JB, Kabagambe EK, Khalifa SE, Kengne AP, Khader YS, Khang YH, Kim D, Kimokoti RW, Kinge JM, Kokubo Y, Kosen S, Kwan G, Lai T, Leinsalu M, Li Y, Liang X, Liu S, Logroscino G, Lotufo PA, Lu Y, Ma J, Mainoo NK, Mensah GA, Merriman TR, Mokdad AH, Moschandreas J, Naghavi M, Naheed A, Nand D, Narayan KM, Nelson EL, Neuhouser ML, Nisar MI, Ohkubo T, Oti SO, Pedroza A, Prabhakaran D, Roy N, Sampson U, Seo H, Sepanlou SG, Shibuya K, Shiri R, Shiue I, Singh GM, Singh JA, Skirbekk V, Stapelberg NJ, Sturua L, Sykes BL, Tobias M, Tran BX, Trasande L, Toyoshima H, van de Vijver S, Vasankari TJ, Veerman JL, Velasquez-Melendez G, Vlassov VV, Vollset SE, Vos T, Wang C, Wang X, Weiderpass E, Werdecker A, Wright JL, Yang YC, Yatsuya H, Yoon J, Yoon SJ, Zhao Y, Zhou M, Zhu S, Lopez AD, Murray CJ, Gakidou E. Global, regional, and national prevalence of overweight and obesity in children and adults during 2014. The Lancet 2014;384:766–81.10.1016/S0140-6736(14)60460-8Suche in Google Scholar

117. Calle E, Thun M. Obesity and cancer. Oncogene 2004;23:6365–78.10.1038/sj.onc.1207751Suche in Google Scholar PubMed

118. Gong Z, Agalliu I, Lin DW, Stanford JL, Kristal AR. Obesity is associated with increased risks of prostate cancer metastasis and death after initial cancer diagnosis in middle-aged men. Cancer 2007;109:1192–202.10.1002/cncr.22534Suche in Google Scholar PubMed

119. Wolin KY, Carson K, Colditz GA. Obesity and cancer. Oncologist 2010;15:556–65.10.1634/theoncologist.2009-0285Suche in Google Scholar PubMed PubMed Central

120. Reeves GK, Pirie K, Beral V, Green J, Spencer E, Bull D, Million Women Study C. Cancer incidence and mortality in relation to body mass index in the Million Women Study: cohort study. Br Med J 2007;335:1314.10.1136/bmj.39367.495995.AESuche in Google Scholar PubMed PubMed Central

121. Gibson TM, Park Y, Robien K, Shiels MS, Black A, Sampson JN, Purdue MP, Beane Freeman LE, Andreotti G, Weinstein SJ, Albanes D, Fraumeni JF Jr., Curtis RE, Berrington de Gonzalez A, Morton LM. Body mass index and risk of second obesity-associated cancers after colorectal cancer: a pooled analysis of prospective cohort studies. J Clin Oncol 2014;32:4004–11.10.1200/JCO.2014.56.8444Suche in Google Scholar PubMed PubMed Central

122. Kaidar-Person O, Bar-Sela G, Person B. The two major epidemics of the twenty-first century: obesity and cancer. Obes Surg 2011;21:1792–7.10.1007/s11695-011-0490-2Suche in Google Scholar PubMed

123. Kitahara CM, Platz EA, Freeman LE, Hsing AW, Linet MS, Park Y, Schairer C, Schatzkin A, Shikany JM, Berrington de González A. Obesity and thyroid cancer risk among U.S. men and women: a pooled analysis of five prospective studies. Cancer Epidemiol Biomarkers Prev 2011;20:464–72.10.1158/1055-9965.EPI-10-1220Suche in Google Scholar PubMed PubMed Central

124. Lichtman MA. Obesity and the risk for a hematological malignancy: leukemia, lymphoma, or myeloma. Oncologist 2010;15:1083–101.10.1634/theoncologist.2010-0206Suche in Google Scholar PubMed PubMed Central

125. Greenberg AS, Obin MS. Obesity and the role of adipose tissue in inflammation and metabolism. Am J Clin Nutr 2006;83:461S–5S.10.1093/ajcn/83.2.461SSuche in Google Scholar PubMed

126. Nieman KM, Romero IL, Van Houten B, Lengyel E. Adipose tissue and adipocytes support tumorigenesis and metastasis. Biochim Biophys Acta 2013;1831:1533–41.10.1016/j.bbalip.2013.02.010Suche in Google Scholar PubMed PubMed Central

127. Vona-Davis L, Rose DP. Adipokines as endocrine, paracrine, and autocrine factors in breast cancer risk and progression. Endocr Relat Cancer 2007;14:189–206.10.1677/ERC-06-0068Suche in Google Scholar PubMed

128. Hoon Kim J, Lee SY, Myung SC, Kim YS, Kim T-H, Kim MK. Clinical significance of the leptin and leptin receptor expressions in prostate tissues. Asian J Androl 2008;10:923–8.10.1111/j.1745-7262.2008.00438.xSuche in Google Scholar PubMed

129. Tewari R, Rajender S, Natu SM, Goel A, Dalela D, Goel MM, Tondon P. Significance of obesity markers and adipocytokines in high grade and high stage prostate cancer in North Indian men – a cross-sectional study. Cytokine 2013;63:130–4.10.1016/j.cyto.2013.04.008Suche in Google Scholar PubMed

130. Ribeiro R, Vasconcelos A, Costa S, Pinto D, Morais A, Oliveira J, Lobo F, Lopes C, Medeiros R. Overexpressing leptin genetic polymorphism (?2548 G/A) is associated with susceptibility to prostate cancer and risk of advanced disease. Prostate 2004;59:268–74.10.1002/pros.20004Suche in Google Scholar PubMed

131. Margetic S, Gazzola C, Pegg GG, Hill RA. Leptin: a review of its peripheral actions and interactions. Int J Obes Relat Metab Disord 2002;26:1407–33.10.1038/sj.ijo.0802142Suche in Google Scholar PubMed

132. Muoio DM, Lynis Dohm G. Peripheral metabolic actions of leptin. Best Pract Res Clin Endocrinol Metab 2002;16:653–66.10.1053/beem.2002.0223Suche in Google Scholar PubMed

133. Garofalo C, Koda M, Cascio S, Sulkowska M, Kanczuga-Koda L, Golaszewska J, Russo A, Sulkowski S, Surmacz E. Increased expression of leptin and the leptin receptor as a marker of breast cancer progression: possible role of obesity-related stimuli. Clin Cancer Res 2006;12:1447–53.10.1158/1078-0432.CCR-05-1913Suche in Google Scholar PubMed

134. Ishikawa M, Kitayama J, Nagawa H. Enhanced expression of leptin and leptin receptor (OB-R) in human breast cancer. Clin Cancer Res 2004;10:4325–31.10.1158/1078-0432.CCR-03-0749Suche in Google Scholar PubMed

135. Dong Z, Fu S, Xu X, Yang Y, Du L, Li W, Kan S, Li Z, Zhang X, Wang L, Li J, Liu H, Qu X, Wang C. Leptin-mediated regulation of ICAM-1 is Rho/ROCK dependent and enhances gastric cancer cell migration. Br J Cancer 2014;110:1801–10.10.1038/bjc.2014.70Suche in Google Scholar PubMed PubMed Central

136. Yehuda-Shnaidman E, Nimri L, Tarnovscki T, Kirshtein B, Rudich A, Schwartz B. Secreted human adipose leptin decreases mitochondrial respiration in HCT116 colon cancer cells. PLoS ONE 2013;8:e74843.10.1371/journal.pone.0074843Suche in Google Scholar PubMed PubMed Central

137. Dalamaga M, Diakopoulos KN, Mantzoros CS. The role of adiponectin in cancer: a review of current evidence. Endocrine Rev 2012;33:547–94.10.1210/er.2011-1015Suche in Google Scholar PubMed PubMed Central

138. Goktas S, Yilmaz MI, Caglar K, Sonmez A, Kilic S, Bedir S. Prostate cancer and adiponectin. Urology 2005;65:1168–72.10.1016/j.urology.2004.12.053Suche in Google Scholar PubMed

139. Brakenhielm E, Veitonmaki N, Cao R, Kihara S, Matsuzawa Y, Zhivotovsky B, Funahashi T, Cao Y. Adiponectin-induced antiangiogenesis and antitumor activity involve caspase-mediated endothelial cell apoptosis. Proc Natl Acad Sci USA 2004;101: 2476–81.10.1073/pnas.0308671100Suche in Google Scholar PubMed PubMed Central

140. Yokota T, Oritani K, Takahashi I, Ishikawa J, Matsuyama A, Ouchi N, Kihara S, Funahashi T, Tenner AJ, Tomiyama Y, Matsuzawa Y. Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood 2000;96:1723–32.10.1182/blood.V96.5.1723Suche in Google Scholar

141. Kang JH, Lee YY, Yu BY, Yang B-S, Cho K-H, Yoon DK, Roh YK. Adiponectin induces growth arrest and apoptosis of MDA-MB-231 breast cancer cell. Arch Pharm Res 2005;28:1263–9.10.1007/BF02978210Suche in Google Scholar PubMed

142. Dieudonne M-N, Bussiere M, Dos Santos E, Leneveu M-C, Giudicelli Y, Pecquery R. Adiponectin mediates antiproliferative and apoptotic responses in human MCF7 breast cancer cells. Biochem Biophys Res Commun 2006;345:271–9.10.1016/j.bbrc.2006.04.076Suche in Google Scholar PubMed

143. Bub JD, Miyazaki T, Iwamoto Y. Adiponectin as a growth inhibitor in prostate cancer cells. Biochem Biophys Res Commun 2006;340:1158–66.10.1016/j.bbrc.2005.12.103Suche in Google Scholar PubMed

144. Suzuki S, Wilson-Kubalek EM, Wert D, Tsao TS, Lee DH. The oligomeric structure of high molecular weight adiponectin. FEBS Lett 2007;581:809–14.10.1016/j.febslet.2007.01.046Suche in Google Scholar PubMed PubMed Central

145. Calle EE, Kaaks R. Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer 2004;4:579–91.10.1038/nrc1408Suche in Google Scholar PubMed

146. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011;61:69–90.10.3322/caac.20107Suche in Google Scholar PubMed

147. Vucenik I, Stains JP. Obesity and cancer risk: evidence, mechanisms, and recommendations. Ann N Y Acad Sci 2012;1271:37–43.10.1111/j.1749-6632.2012.06750.xSuche in Google Scholar PubMed PubMed Central

148. Herroon MK, Rajagurubandara E, Hardaway AL, Powell K, Turchick A, Feldmann D, Podgorski I. Bone marrow adipocytes promote tumor growth in bone via FABP4-dependent mechanisms. Oncotarget 2013;4:2108–23.10.18632/oncotarget.1482Suche in Google Scholar PubMed PubMed Central

149. Gazi E, Gardner P, Lockyer NP, Hart CA, Brown MD, Clarke NW. Direct evidence of lipid translocation between adipocytes and prostate cancer cells with imaging FTIR microspectroscopy. J Lipid Res 2007;48:1846–56.10.1194/jlr.M700131-JLR200Suche in Google Scholar PubMed

150. Tokuda Y, Satoh Y, Fujiyama C, Toda S, Sugihara H, Masaki Z. Prostate cancer cell growth is modulated by adipocyte-cancer cell interaction. BJU Int 2003;91:716–20.10.1046/j.1464-410X.2003.04218.xSuche in Google Scholar

151. Brown MD, Hart CA, Gazi E, Bagley S, Clarke NW. Promotion of prostatic metastatic migration towards human bone marrow stoma by Omega 6 and its inhibition by Omega 3 PUFAs. Br J Cancer 2006;94:842–53.10.1038/sj.bjc.6603030Suche in Google Scholar PubMed PubMed Central

152. Hardaway AL, Podgorski I. IL-1beta, RAGE and FABP4: targeting the dynamic trio in metabolic inflammation and related pathologies. Future Med Chem 2013;5:1089–108.10.4155/fmc.13.90Suche in Google Scholar PubMed PubMed Central

153. Nieman KM, Kenny HA, Penicka CV, Ladanyi A, Buell-Gutbrod R, Zillhardt MR, Romero IL, Carey MS, Mills GB, Hotamisligil GS, Yamada SD, Peter ME, Gwin K, Lengyel E. Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth. Nat Med 2011;17:1498–503.10.1038/nm.2492Suche in Google Scholar PubMed PubMed Central

154. Liu Y. Fatty acid oxidation is a dominant bioenergetic pathway in prostate cancer. Prostate Cancer Prostatic Dis 2006;9:230–4.10.1038/sj.pcan.4500879Suche in Google Scholar PubMed

155. Akram M. Mini-review on glycolysis and cancer. J Cancer Educ 2013;28:454–7.10.1007/s13187-013-0486-9Suche in Google Scholar PubMed

156. Jones RG, Thompson CB. Tumor suppressors and cell metabolism: a recipe for cancer growth. Genes Dev 2009;23:537–48.10.1101/gad.1756509Suche in Google Scholar PubMed PubMed Central

157. Warburg O. On the origin of cancer cells. Science 1956;123:309–14.10.1126/science.123.3191.309Suche in Google Scholar PubMed

158. Baron A, Migita T, Tang D, Loda M. Fatty acid synthase: a metabolic oncogene in prostate cancer? J Cell Biochem 2004;91:47–53.10.1002/jcb.10708Suche in Google Scholar PubMed

159. Brown GC. Control of respiration and ATP synthesis in mammalian mitochondria and cells. Biochem J 1992;284:1–13.10.1042/bj2840001Suche in Google Scholar PubMed PubMed Central

160. Cairns RA, Harris IS, Mak TW. Regulation of cancer cell metabolism. Nat Rev Cancer 2011;11:85–95.10.1038/nrc2981Suche in Google Scholar PubMed

161. Levine AJ, Puzio-Kuter AM. The control of the metabolic switch in cancers by oncogenes and tumor suppressor genes. Science 2010;330:1340–4.10.1126/science.1193494Suche in Google Scholar PubMed

162. Kim J-W, Dang CV. Multifaceted roles of glycolytic enzymes. Trends Biochem Sci 2005;30:142–50.10.1016/j.tibs.2005.01.005Suche in Google Scholar PubMed

163. Majewski N, Nogueira V, Bhaskar P, Coy PE, Skeen JE, Gottlob K, Chandel NS, Thompson CB, Robey RB, Hay N. Hexokinase-mitochondria interaction mediated by Akt is required to inhibit apoptosis in the presence or absence of Bax and Bak. Mol Cell 2004;16:819–30.10.1016/j.molcel.2004.11.014Suche in Google Scholar PubMed

164. Pastorino JG, Shulga N, Hoek JB. Mitochondrial binding of hexokinase II inhibits Bax-induced cytochrome c release and apoptosis. J Biol Chem 2002;277:7610–8.10.1074/jbc.M109950200Suche in Google Scholar PubMed

165. Sun L, Shukair S, Naik TJ, Moazed F, Ardehali H. Glucose phosphorylation and mitochondrial binding are required for the protective effects of hexokinases I and II. Mol Cell Biol 2008;28:1007–17.10.1128/MCB.00224-07Suche in Google Scholar PubMed PubMed Central

166. Tamada M, Suematsu M, Saya H. Pyruvate kinase M2: multiple faces for conferring benefits on cancer cells. Clin Cancer Res 2012;18:5554–61.10.1158/1078-0432.CCR-12-0859Suche in Google Scholar PubMed

167. Lu Z. Nonmetabolic functions of pyruvate kinase isoform M2 in controlling cell cycle progression and tumorigenesis. Chin J Cancer 2012;31:5–7.Suche in Google Scholar

168. Matsumoto S, Kishida K, Shimomura I, Maeda N, Nagaretani H, Matsuda M, Nishizawa H, Kihara S, Funahashi T, Matsuzawa Y, Yamada A, Yamashita S, Tamura S, Kawata S. Increased plasma HB-EGF associated with obesity and coronary artery disease. Biochem Biophys Res Commun 2002;292:781–6.10.1006/bbrc.2002.6720Suche in Google Scholar PubMed

169. Henriksen L, Grandal MV, Knudsen SLJ, van Deurs B, Grøvdal LM. Internalization mechanisms of the epidermal growth factor receptor after activation with different ligands. PLoS One 2013;8:e58148.10.1371/journal.pone.0058148Suche in Google Scholar PubMed PubMed Central

170. Yang W, Xia Y, Hawke D, Li X, Liang J, Xing D, Aldape K, Hunter T, Alfred Yung WK, Lu Z. PKM2 phosphorylates histone H3 and promotes gene transcription and tumorigenesis. Cell 2012;150:685–96.10.1016/j.cell.2012.07.018Suche in Google Scholar PubMed PubMed Central

171. Lee J, Kim HK, Han Y-M, Kim J. Pyruvate kinase isozyme type M2 (PKM2) interacts and cooperates with Oct-4 in regulating transcription. Int J Biochem Cell Biol 2008;40:1043–54.10.1016/j.biocel.2007.11.009Suche in Google Scholar PubMed

172. Morfouace M, Lalier L, Oliver L, Cheray M, Pecqueur C, Cartron PF, Vallette FM. Control of lioma cell death and differentiation by PKM2-Oct4 interaction. Cell Death Dis 2014;5:e1036. doi: 10.1038/cddis.2013.561.10.1038/cddis.2013.561Suche in Google Scholar PubMed PubMed Central

173. DeBerardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB. The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab 2008;7:11–20.10.1016/j.cmet.2007.10.002Suche in Google Scholar PubMed

174. Gatenby RA, Gillies RJ. Why do cancers have high aerobic glycolysis? Nat Rev Cancer 2004;4:891–9.10.1038/nrc1478Suche in Google Scholar PubMed

175. Cairns RA, Bennewith KL, Graves EE, Giaccia AJ, Chang DT, Denko NC. Pharmacologically increased tumor hypoxia can be measured by 18F-Fluoroazomycin arabinoside positron emission tomography and enhances tumor response to hypoxic cytotoxin PR-104. Clin Cancer Res 2009;15:7170–4.10.1158/1078-0432.CCR-09-1676Suche in Google Scholar PubMed PubMed Central

176. Michelakis ED, Sutendra G, Dromparis P, Webster L, Haromy A, Niven E, Maguire C, Gammer TL, Mackey JR, Fulton D, Abdulkarim B, McMurtry MS, Petruk KC. Metabolic modulation of glioblastoma with dichloroacetate. Sci Transl Med 2010;2:31ra34.10.1126/scitranslmed.3000677Suche in Google Scholar PubMed

177. Soga T. Cancer metabolism: key players in metabolic reprogramming. Cancer Sci 2013;104:275–81.10.1111/cas.12085Suche in Google Scholar PubMed PubMed Central

178. Husain Z, Huang Y, Seth P, Sukhatme VP. Tumor-derived lactate modifies antitumor immune response: effect on myeloid-derived suppressor cells and NK cells. J Immunol 2013;191:1486–95.10.4049/jimmunol.1202702Suche in Google Scholar PubMed

179. Beckert S, Farrahi F, Aslam RS, Scheuenstuhl H, Konigsrainer A, Hussain MZ, Hunt TK. Lactate stimulates endothelial cell migration. Wound Repair Regen 2006;14:321–4.10.1111/j.1743-6109.2006.00127.xSuche in Google Scholar PubMed

180. Polet F, Feron O. Endothelial cell metabolism and tumour angiogenesis: glucose and glutamine as essential fuels and lactate as the driving force. J Intern Med 2013;273:156–65.10.1111/joim.12016Suche in Google Scholar PubMed

181. Shim H, Dolde C, Lewis BC, Wu CS, Dang G, Jungmann RA, Dalla-Favera R, Dang CV. c-Myc transactivation of LDH-A: implications for tumor metabolism and growth. Proc Natl Acad Sci USA 1997;94:6658–63.10.1073/pnas.94.13.6658Suche in Google Scholar PubMed PubMed Central

182. Kim Jw, Zeller KI, Wang Y, Jegga AG, Aronow BJ, O’Donnell KA, Dang CV. Evaluation of Myc E-Box phylogenetic footprints in glycolytic genes by chromatin immunoprecipitation assays. Mol Cell Biol 2004;24:5923–36.10.1128/MCB.24.13.5923-5936.2004Suche in Google Scholar PubMed PubMed Central

183. Mannava S, Grachtchouk V, Wheeler LJ, Im M, Zhuang D, Slavina EG, Mathews CK, Shewach DS, Nikiforov MA. Direct role of nucleotide metabolism in C-MYC-dependent proliferation of melanoma cells. Cell Cycle 2008;7: 2392–400.10.4161/cc.6390Suche in Google Scholar PubMed PubMed Central

184. Liu Y-C, Li F, Handler J, Huang CRL, Xiang Y, Neretti N, Sedivy JM, Zeller KI, Dang CV. Global regulation of nucleotide biosynthetic genes by c-Myc. PLoS One 2008;3:e2722.10.1371/journal.pone.0002722Suche in Google Scholar PubMed PubMed Central

185. David CJ, Chen M, Assanah M, Canoll P, Manley JL. HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer. Nature 2010;463:364–8.10.1038/nature08697Suche in Google Scholar PubMed PubMed Central

186. Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975–2011, Bethesda, MD: National Cancer Institute. http://seer.cancer.gov/csr/1975_2011/, based on November 2013 SEER data submission, posted to the SEER web site, April 2014.Suche in Google Scholar

187. Christofk HR, Vander Heiden MG, Harris MH, Ramanathan A, Gerszten RE, Wei R, Fleming MD, Schreiber SL, Cantley LC. The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature 2008;452:230–3.10.1038/nature06734Suche in Google Scholar PubMed

188. Clower CV, Chatterjee D, Wang Z, Cantley LC, Vander Heiden MG, Krainer AR. The alternative splicing repressors hnRNP A1/A2 and PTB influence pyruvate kinase isoform expression and cell metabolism. Proc Natl Acad Sci USA 2010;107:1894–9.10.1073/pnas.0914845107Suche in Google Scholar PubMed PubMed Central

189. Wong N, De Melo J, Tang D. PKM2, a central point of regulation in cancer metabolism. Int J Cell Biol 2013;2013:1–11.10.1155/2013/242513Suche in Google Scholar PubMed PubMed Central

190. Vita M, Henriksson M. The Myc oncoprotein as a therapeutic target for human cancer. Semin Cancer Biol 2006;16:318–30.10.1016/j.semcancer.2006.07.015Suche in Google Scholar PubMed

191. Liu H, Radisky DC, Yang D, Xu R, Radisky ES, Bissell MJ, Bishop JM. MYC suppresses cancer metastasis by direct transcriptional silencing of alphav and beta3 integrin subunits. Nat Cell Biol 2012;14:567–74.10.1038/ncb2491Suche in Google Scholar PubMed PubMed Central

192. Boland ML, Chourasia AH, Macleod KF. Mitochondrial dysfunction in cancer. Front Oncol 2013;3:292.10.3389/fonc.2013.00292Suche in Google Scholar PubMed PubMed Central

193. Kaaman M, Sparks LM, van Harmelen V, Smith SR, Sjolin E, Dahlman I, Arner P. Strong association between mitochondrial DNA copy number and lipogenesis in human white adipose tissue. Diabetologia 2007;50:2526–33.10.1007/s00125-007-0818-6Suche in Google Scholar PubMed

194. Compton S, Kim C, Griner NB, Potluri P, Scheffler IE, Sen S, Jerry DJ, Schneider S, Yadava N. Mitochondrial dysfunction impairs tumor suppressor p53 expression/function. J Biol Chem 2011;286:20297–312.10.1074/jbc.M110.163063Suche in Google Scholar PubMed PubMed Central

195. Bournat JC, Brown CW. Mitochondrial dysfunction in obesity. Curr Opin Endocrinol Diabetes Obes 2010;17:446–52.10.1097/MED.0b013e32833c3026Suche in Google Scholar PubMed PubMed Central

196. Robey IF, Lien AD, Welsh SJ, Baggett BK, Gillies RJ. Hypoxia-inducible factor-1alpha and the glycolytic phenotype in tumors. Neoplasia 2005;7:324–30.10.1593/neo.04430Suche in Google Scholar PubMed PubMed Central

197. Benizri E, Ginouves A, Berra E. The magic of the hypoxia-signaling cascade. Cell Mol Life Sci 2008;65:1133–49.10.1007/s00018-008-7472-0Suche in Google Scholar

198. Bruick RK. Oxygen sensing in the hypoxic response pathway: regulation of the hypoxia-inducible transcription factor. Genes Dev 2003;17:2614–23.10.1101/gad.1145503Suche in Google Scholar

199. Semenza GL. Targeting HIF-1 for cancer therapy. Nat Rev 2003;3:721–32.10.1038/nrc1187Suche in Google Scholar

200. Ogawa K, Chiba I, Morioka T, Shimoji H, Tamaki W, Takamatsu R, Nishimaki T, Yoshimi N, Murayama S. Clinical significance of HIF-1alpha expression in patients with esophageal cancer treated with concurrent chemoradiotherapy. Anticancer Res 2011;31:2351–9.Suche in Google Scholar

201. Vaupel P, Mayer A, Höckel M. Tumor hypoxia and malignant progression. Meth Enzymol 2004;381:335–54.10.1016/S0076-6879(04)81023-1Suche in Google Scholar

202. Semenza GL. Defining the role of hypoxia-inducible factor 1 in cancer biology and herapeutics. Oncogene 2010;29:625–34.10.1038/onc.2009.441Suche in Google Scholar PubMed PubMed Central

203. Semenza GL. HIF-1 mediates metabolic responses to intratumoral hypoxia and oncogenic mutations. J Clin Invest 2013;123:3664–71.10.1172/JCI67230Suche in Google Scholar PubMed PubMed Central

204. Hu CJ, Wang LY, Chodosh LA, Keith B, Simon MC. Differential roles of hypoxia-inducible factor 1 (HIF-1) and HIF-2 in hypoxic gene regulation. Mol Cell Biol 2003;23:9361–74.10.1128/MCB.23.24.9361-9374.2003Suche in Google Scholar PubMed PubMed Central

205. Luo W, Hu H, Chang R, Zhong J, Knabel M, O’Meally R, Cole Robert N, Pandey A, Semenza GL. Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1. Cell 2011;145:732–44.10.1016/j.cell.2011.03.054Suche in Google Scholar PubMed PubMed Central

206. Wang H-J, Hsieh Y-J, Cheng W-C, Lin C-P, Lin Y-s, Yang S-F, Chen C-C, Izumiya Y, Yu J-S, Kung H-J, Wang W-C. JMJD5 regulates PKM2 nuclear translocation and reprograms HIF-1α-mediated glucose metabolism. Proc Natl Acad Sci USA 2014;111:279–84.10.1073/pnas.1311249111Suche in Google Scholar PubMed PubMed Central

207. Hsia DA, Tepper CG, Pochampalli MR, Hsia EYC, Izumiya C, Huerta SB, Wright ME, Chen H-W, Kung H-J, Izumiya Y. KDM8, a H3K36me2 histone demethylase that acts in the cyclin A1 coding region to regulate cancer cell proliferation. Proc Natl Acad Sci USA 2010;107:9671–6.10.1073/pnas.1000401107Suche in Google Scholar PubMed PubMed Central

208. Ivan M, Harris AL, Martelli F, Kulshreshtha R. Hypoxia response and microRNAs: no longer two separate worlds. J Cell Mol Med 2008;12:1426–31.10.1111/j.1582-4934.2008.00398.xSuche in Google Scholar PubMed PubMed Central

209. Macfarlane LA, Murphy PR. MicroRNA: biogenesis, function and role in cancer. Curr Genom 2010;11:537–61.10.2174/138920210793175895Suche in Google Scholar PubMed PubMed Central

210. Devlin C, Greco S, Martelli F, Ivan M. miR-210: More than a silent player in hypoxia. IUBMB Life 2011;63:94–100.10.1002/iub.427Suche in Google Scholar PubMed PubMed Central

211. Chan SY, Zhang Y-Y, Hemann C, Mahoney CE, Zweier JL, Loscalzo J. MicroRNA-210 controls mitochondrial metabolism during hypoxia by repressing the iron-sulfur cluster assembly proteins ISCU1/2. Cell Metab 2009;10:273–84.10.1016/j.cmet.2009.08.015Suche in Google Scholar PubMed PubMed Central

212. Chen Z, Li Y, Zhang H, Huang P, Luthra R. Hypoxia-regulated microRNA-210 modulates mitochondrial function and decreases ISCU and COX10 expression. Oncogene 2010;29:4362–8.10.1038/onc.2010.193Suche in Google Scholar PubMed

213. Grosso S, Doyen J, Parks SK, Bertero T, Paye A, Cardinaud B, Gounon P, Lacas-Gervais S, Noël A, Pouysségur J, Barbry P, Mazure NM, Mari B. MiR-210 promotes a hypoxic phenotype and increases radioresistance in human lung cancer cell lines. Cell Death Dis 2013;4:e544.10.1038/cddis.2013.71Suche in Google Scholar PubMed PubMed Central

214. Puisségur MP, Mazure NM, Bertero T, Pradelli L, Grosso S, Robbe-Sermesant K, Maurin T, Lebrigand K, Cardinaud B, Hofman V, Fourre S, Magnone V, Ricci JE, Pouysségur J, Gounon P, Hofman P, Barbry P, Mari B. miR-210 is overexpressed in late stages of lung cancer and mediates mitochondrial alterations associated with modulation of HIF-1 activity. Cell Death Differ 2011;18:465–78.10.1038/cdd.2010.119Suche in Google Scholar PubMed PubMed Central

215. Camps C, Buffa FM, Colella S, Moore J, Sotiriou C, Sheldon H, Harris AL, Gleadle JM, Ragoussis J. hsa-miR-210 is induced by hypoxia and is an independent prognostic factor in breast cancer. Clin Cancer Res 2008;14:1340–8.10.1158/1078-0432.CCR-07-1755Suche in Google Scholar PubMed

216. Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med 1971;285:1182–6.10.1056/NEJM197111182852108Suche in Google Scholar PubMed

217. Holmgren L, O’Reilly MS, Folkman J. Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression. Nat Med 1995;1:149–53.10.1038/nm0295-149Suche in Google Scholar PubMed

218. Parangi S, O’Reilly M, Christofori G, Holmgren L, Grosfeld J, Folkman J, Hanahan D. Antiangiogenic therapy of transgenic mice impairs de novo tumor growth. Proc Natl Acad Sci USA 1996;93:2002–7.10.1073/pnas.93.5.2002Suche in Google Scholar PubMed PubMed Central

219. Forsythe JA, Jiang BH, Iyer NV, Agani F, Leung SW, Koos RD, Semenza GL. Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol Cell Biol 1996;16:4604–13.10.1128/MCB.16.9.4604Suche in Google Scholar PubMed PubMed Central

220. Zhang P, Wang Y, Hui Y, Hu D, Wang H, Zhou J, Du H. Inhibition of VEGF expression by targeting HIF-1 alpha with small interference RNA in human RPE cells. Ophthalmologica 2007;221:411–7.10.1159/000107502Suche in Google Scholar PubMed

221. Hosogai N, Fukuhara A, Oshima K, Miyata Y, anaka S, Segawa K, Furukawa S, Tochino Y, Komuro R, Matsuda M, Shimomura I. Adipose tissue hypoxia in obesity and its impact on adipocytokine dysregulation. Diabetes 2007;56:901–11.10.2337/db06-0911Suche in Google Scholar PubMed

222. Yin J, Gao Z, He Q, Zhou D, Guo Z, Ye J. Role of hypoxia in obesity-induced disorders of glucose and lipid metabolism in adipose tissue. Am J Physiol 2009;296:E333–42.10.1152/ajpendo.90760.2008Suche in Google Scholar PubMed PubMed Central

223. Pasarica M, Sereda OR, Redman LM, Albarado DC, Hymel DT, Roan LE, Rood JC, Burk DH, Smith SR. Reduced adipose tissue oxygenation in human obesity: evidence for rarefaction, macrophage chemotaxis, and inflammation without an angiogenic response. Diabetes 2009;58:718–25.10.2337/db08-1098Suche in Google Scholar PubMed PubMed Central

224. Rausch ME, Weisberg S, Vardhana P, Tortoriello DV. Obesity in C57BL/6J mice is characterized by adipose tissue hypoxia and cytotoxic T-cell infiltration. Int J Obes 2008;32:451–63.10.1038/sj.ijo.0803744Suche in Google Scholar PubMed

225. Elias I, Franckhauser S, Ferre T, Vila L, Tafuro S, Munoz S, Roca C, Ramos D, Pujol A, Riu E, Ruberte J, Bosch F. Adipose tissue overexpression of vascular endothelial growth factor protects against diet-induced obesity and insulin resistance. Diabetes 2012;61:1801–13.10.2337/db11-0832Suche in Google Scholar PubMed PubMed Central

226. Liang Y, Brekken RA, Hyder SM. Vascular endothelial growth factor induces proliferation of breast cancer cells and inhibits the anti-proliferative activity of anti-hormones. Endocr Relat Cancer 2006;13:905–19.10.1677/erc.1.01221Suche in Google Scholar PubMed

227. Goel HL, Mercurio AM. VEGF targets the tumour cell. Nat Rev Cancer 2013:13:871–82.10.1038/nrc3627Suche in Google Scholar PubMed PubMed Central

228. Lee AS. GRP78 induction in cancer: therapeutic and prognostic implications. Cancer Res 2007;67:3496–9.10.1158/0008-5472.CAN-07-0325Suche in Google Scholar PubMed

229. Yuzefovych LV, Musiyenko SI, Wilson GL, Rachek LI. Mitochondrial DNA damage and dysfunction, and oxidative stress are associated with endoplasmic reticulum stress, protein degradation and apoptosis in high fat diet-induced insulin resistance mice. PLoS One 2013;8:e54059.10.1371/journal.pone.0054059Suche in Google Scholar PubMed PubMed Central

230. Bi M, Naczki C, Koritzinsky M, Fels D, Blais J, Hu N, Harding H, Novoa I, Varia M, Raleigh J, Scheuner D, Kaufman RJ, Bell J, Ron D, Wouters BG, Koumenis C. ER stress-regulated translation increases tolerance to extreme hypoxia and promotes tumor growth. EMBO J 2005;24:3470–81.10.1038/sj.emboj.7600777Suche in Google Scholar PubMed PubMed Central

231. Romero-Ramirez L, Cao H, Nelson D, Hammond E, Lee AH, Yoshida H, Mori K, Glimcher LH, Denko NC, Giaccia AJ, Le QT, Koong AC. XBP1 is essential for survival under hypoxic conditions and is required for tumor growth. Cancer Res 2004;64:5943–7.10.1158/0008-5472.CAN-04-1606Suche in Google Scholar PubMed

232. Rouschop KM, van den Beucken T, Dubois L, Niessen H, Bussink J, Savelkouls K, Keulers T, Mujcic H, Landuyt W, Voncken JW, Lambin P, van der Kogel AJ, Koritzinsky M, Wouters BG. The unfolded protein response protects human tumor cells during hypoxia through regulation of the autophagy genes MAP1LC3B and ATG5. J Clin Invest 2010;120:127–41.10.1172/JCI40027Suche in Google Scholar PubMed PubMed Central

233. Mujcic H, Nagelkerke A, Rouschop KM, Chung S, Chaudary N, Span PN, Clarke B, Milosevic M, Sykes J, Hill RP, Koritzinsky M, Wouters BG. Hypoxic activation of the PERK/eIF2alpha arm of the unfolded protein response promotes metastasis through induction of LAMP3. Clin Cancer Res 2013;19:6126–37.10.1158/1078-0432.CCR-13-0526Suche in Google Scholar PubMed

234. Martinon F. Targeting endoplasmic reticulum signaling pathways in cancer. Acta Oncol 2012;51:822–30.10.3109/0284186X.2012.689113Suche in Google Scholar PubMed

235. Healy SJ, Gorman AM, Mousavi-Shafaei P, Gupta S, Samali A. Targeting the endoplasmic reticulum-stress response as an anticancer strategy. Eur J Pharmacol 2009;625:234–46.10.1016/j.ejphar.2009.06.064Suche in Google Scholar PubMed

236. Ma Y, Hendershot LM. The role of the unfolded protein response in tumour development: friend or foe? Nat Rev Cancer 2004;4:966–77.10.1038/nrc1505Suche in Google Scholar PubMed

237. Chen X, Iliopoulos D, Zhang Q, Tang Q, Greenblatt MB, Hatziapostolou M, Lim E, Tam WL, Ni M, Chen Y, Mai J, Shen H, Hu DZ, Adoro S, Hu B, Song M, Tan C, Landis MD, Ferrari M, Shin SJ, Brown M, Chang JC, Liu XS, Glimcher LH. XBP1 promotes triple-negative breast cancer by controlling the HIF1α pathway. Nature 2014;508:103–7.10.1038/nature13119Suche in Google Scholar PubMed PubMed Central

238. Pereira ER, Frudd K, Awad W, Hendershot LM. Endoplasmic reticulum (ER) stress and hypoxia response pathways interact to potentiate hypoxia-inducible factor 1 (HIF-1) transcriptional activity on targets like vascular endothelial growth factor (VEGF). J Biol Chem 2014;289:3352–64.10.1074/jbc.M113.507194Suche in Google Scholar PubMed PubMed Central

239. Koumenis C. ER stress, hypoxia tolerance and tumor progression. Curr Mol Med 2006;6:55–69.10.2174/156652406775574604Suche in Google Scholar PubMed

240. Balistreri CR, Caruso C, Candore G. The role of adipose tissue and adipokines in obesity-related inflammatory diseases. Media inflam 2010;2010:802078.10.1155/2010/802078Suche in Google Scholar PubMed PubMed Central

241. Khan S, Shukla S, Sinha S, Meeran SM. Role of adipokines and cytokines in obesity-associated breast cancer: therapeutic targets. Cytokine Growth Factor Rev 2013;24:503–13.10.1016/j.cytogfr.2013.10.001Suche in Google Scholar PubMed

242. García-Ruiz I, Rodríguez-Juan C, Díaz-Sanjuan T, del Hoyo P, Colina F, Mulñoz-Yagüe T, Solís-Herruzo JA. Uric acid and anti-TNF antibody improve mitochondrial dysfunction in ob/ob mice. Hepatology 2006;44:581–91.10.1002/hep.21313Suche in Google Scholar PubMed

243. García-Ruiz I, Solís-Muñoz P, Fernández-Moreira D, Grau M, Colina F, Muñoz-Yagüe T, Solís-Herruzo JA. High-fat diet decreases activity of the oxidative phosphorylation complexes and causes nonalcoholic steatohepatitis in mice. Dis Model Mech 2014;7:1287–96.10.1242/dmm.016766Suche in Google Scholar PubMed PubMed Central

244. Silva-Alvarez C, Arrazola MS, Godoy JA, Ordenes D, Inestrosa NC. Canonical Wnt signaling protects hippocampal neurons from Abeta oligomers: role of non-canonical Wnt-5a/Ca(2+) in mitochondrial dynamics. Front Cell Neurosci 2013;7:97.10.3389/fncel.2013.00097Suche in Google Scholar PubMed PubMed Central

245. Yoon JC, Ng A, Kim BH, Bianco A, Xavier RJ, Elledge SJ. Wnt signaling regulates mitochondrial physiology and insulin sensitivity. Genes Dev 2010;24:1507–18.10.1101/gad.1924910Suche in Google Scholar PubMed PubMed Central

246. Donato J, Frazão R, Elias CF. The PI3K signaling pathway mediates the biological effects of leptin. Arq Bras Endocrinol Metabol 2010;54:591–602.10.1590/S0004-27302010000700002Suche in Google Scholar PubMed

247. Fruman DA, Rommel C. PI3K and cancer: lessons, challenges and opportunities. Nat Rev Drug Discov 2014;13:140–56.10.1038/nrd4204Suche in Google Scholar PubMed PubMed Central

248. Braccini L, Ciraolo E, Martini M, Pirali T, Germena G, Rolfo K, Hirsch E. PI3K keeps the balance between metabolism and cancer. Adv Biol Reg 2012;52:389–405.10.1016/j.jbior.2012.04.002Suche in Google Scholar PubMed

249. Edinger AL. Akt maintains cell size and survival by increasing mTOR-dependent nutrient uptake. Mol Biol Cell 2002;13: 2276–88.10.1091/mbc.01-12-0584Suche in Google Scholar PubMed PubMed Central

250. Jia S, Liu Z, Zhang S, Liu P, Zhang L, Lee SH, Zhang J, Signoretti S, Loda M, Roberts TM, Zhao JJ. Essential roles of PI(3)K–p110β in cell growth, metabolism and tumorigenesis. Nature 2008;454:776–9.10.1038/nature07091Suche in Google Scholar PubMed PubMed Central

251. Lee SY, Jeon HM, Ju MK, Kim CH, Yoon G, Han SI, Park HG, Kang HS. Wnt/Snail signaling regulates cytochrome c oxidase and glucose metabolism. Cancer Res 2012;72:3607–17.10.1158/0008-5472.CAN-12-0006Suche in Google Scholar PubMed

252. Mori H, Prestwich TC, Reid MA, Longo KA, Gerin I, Cawthorn WP, Susulic VS, Krishnan V, Greenfield A, Macdougald OA. Secreted frizzled-related protein 5 suppresses adipocyte mitochondrial metabolism through WNT inhibition. J Clin Invest 2012;122:2405–16.10.1172/JCI63604Suche in Google Scholar PubMed PubMed Central

253. Tan X, Wang X, Chu H, Liu H, Yi X, Xiao Y. SFRP5 correlates with obesity and metabolic syndrome and increases after weight loss in children. Clin Endocrinol 2014;81:363–9.10.1111/cen.12361Suche in Google Scholar PubMed

254. Sekine Y, Suzuki K, Remaley AT. HDL and sphingosine-1-phosphate activate stat3 in prostate cancer DU145 cells via ERK1/2 and S1P receptors, and promote cell migration and invasion. Prostate 2011;71:690–9.10.1002/pros.21285Suche in Google Scholar PubMed PubMed Central

255. Beckham TH, Lu P, Cheng JC, Zhao D, Turner LS, Zhang X, Hoffman S, Armeson KE, Liu A, Marrison T, Hannun YA, Liu X. Acid ceramidase-mediated production of sphingosine 1-phosphate promotes prostate cancer invasion through upregulation of cathepsin B. Int J Cancer 2012;131:2034–43.10.1002/ijc.27480Suche in Google Scholar PubMed PubMed Central

256. Pyne NJ, Pyne S. Sphingosine 1-phosphate and cancer. Nat Rev Cancer 2010;10:489–503.10.1038/nrc2875Suche in Google Scholar PubMed

257. Johnson KR, Johnson KY, Crellin HG, Ogretmen B, Boylan AM, Harley RA, Obeid LM. Immunohistochemical distribution of sphingosine kinase 1 in normal and tumor lung tissue. J Histochem Cytochem 2005;53:1159–66.10.1369/jhc.4A6606.2005Suche in Google Scholar PubMed

258. Van Brocklyn JR, Jackson CA, Pearl DK, Kotur MS, Snyder PJ, Prior TW. Sphingosine kinase-1 expression correlates with poor survival of patients with glioblastoma multiforme: roles of sphingosine kinase isoforms in growth of glioblastoma cell lines. J Neuropathol Exp Neurol 2005;64:695–705.10.1097/01.jnen.0000175329.59092.2cSuche in Google Scholar PubMed

259. Guan H, Liu L, Cai J, Liu J, Ye C, Li M, Li Y. Sphingosine kinase 1 is overexpressed and promotes proliferation in human thyroid cancer. Mol Endocrinol 2011;25:1858–66.10.1210/me.2011-1048Suche in Google Scholar PubMed PubMed Central

260. Watson C, Long JS, Orange C, Tannahill CL, Mallon E, McGlynn LM, Pyne S, Pyne NJ, Edwards J. High expression of sphingosine 1-phosphate receptors, S1P1 and S1P3, sphingosine kinase 1, and extracellular signal-regulated kinase-1/2 is associated with development of tamoxifen resistance in estrogen receptor-positive breast cancer patients. Am J Pathol 2010;177:2205–15.10.2353/ajpath.2010.100220Suche in Google Scholar PubMed PubMed Central

261. Ohotski J, Edwards J, Elsberger B, Watson C, Orange C, Mallon E, Pyne S, Pyne NJ. Identification of novel functional and spatial associations between sphingosine kinase 1, sphingosine 1-phosphate receptors and other signaling proteins that affect prognostic outcome in estrogen receptor-positive breast cancer. Int J Cancer 2013;132:605–16.10.1002/ijc.27692Suche in Google Scholar PubMed

262. Błachnio-Zabielska AU, Pułka M, Baranowski M, Nikołajuk A, Zabielski P, Górska M, Górski J. Ceramide metabolism is affected by obesity and diabetes in human adipose tissue. J Cell Physiol 2012;227:550–7.10.1002/jcp.22745Suche in Google Scholar PubMed

263. Brown J. Effects of 2-deoxyglucose on carbohydrate metablism: review of the literature and studies in the rat. Metab Clin Exp 1962;11:1098–112.Suche in Google Scholar

264. Weindruch R, Keenan KP, Carney JM, Fernandes G, Feuers RJ, Floyd RA, Halter JB, Ramsey JJ, Richardson A, Roth GS, Spindler SR. Caloric restriction mimetics: metabolic interventions. J Gerontol A Biol Sci Med Sci 2001;56:20–33.10.1093/gerona/56.suppl_1.20Suche in Google Scholar PubMed

265. Maher JC, Krishan A, Lampidis TJ. Greater cell cycle inhibition and cytotoxicity induced by 2-deoxy-D-glucose in tumor cells treated under hypoxic vs aerobic conditions. Cancer Chemother Pharmacol 2004;53:116–22.10.1007/s00280-003-0724-7Suche in Google Scholar PubMed

266. Feng X, Zhang Y, Wang P, Liu Q, Wang X. Energy metabolism targeted drugs synergize with photodynamic therapy to potentiate breast cancer cell death. Photochem Photobiol Sci 2014;13:1793–803.10.1039/C4PP00288ASuche in Google Scholar

267. Wang Z, Zhang L, Zhang D, Sun R, Wang Q, Liu X. Glycolysis inhibitor 2-deoxy-D-glucose suppresses carcinogen-induced rat hepatocarcinogenesis by restricting cancer cell metabolism. Mol Med Rep 2014;11:1917–24.10.3892/mmr.2014.2945Suche in Google Scholar PubMed

268. Creighton DJ, Zheng ZB, Holewinski R, Hamilton DS, Eiseman JL. Glyoxalase I inhibitors in cancer chemotherapy. Biochem Society Trans 2003;31 Pt:1378–82.10.1042/bst0311378Suche in Google Scholar PubMed

269. Antognelli C, Palumbo I, Aristei C, Talesa VN. Glyoxalase I inhibition induces apoptosis in irradiated MCF-7 cells via a novel mechanism involving Hsp27, p53 and NF-kappaB. Br J Cancer 2014;111:395–406.10.1038/bjc.2014.280Suche in Google Scholar PubMed PubMed Central

270. Girgis H, Masui O, White NM, Scorilas A, Rotondo F, Seivwright A, Gabril M, Filter ER, Girgis AH, Bjarnason GA, Jewett MA, Evans A, Al-Haddad S, Siu KM, Yousef GM. Lactate dehydrogenase A is a potential prognostic marker in clear cell renal cell carcinoma. Mol Cancer 2014;13:101.10.1186/1476-4598-13-101Suche in Google Scholar PubMed PubMed Central

271. Koukourakis MI, Giatromanolaki A, Sivridis E, Bougioukas G, Didilis V, Gatter KC, Harris AL, Tumour, Angiogenesis Research G. Lactate dehydrogenase-5 (LDH-5) overexpression in non-small-cell lung cancer tissues is linked to tumour hypoxia, angiogenic factor production and poor prognosis. Br J Cancer 2003;89:877–85.10.1038/sj.bjc.6601205Suche in Google Scholar PubMed PubMed Central

272. Miao P, Sheng S, Sun X, Liu J, Huang G. Lactate dehydrogenase A in cancer: a promising target for diagnosis and therapy. IUBMB Life 2013;65:904–10.10.1002/iub.1216Suche in Google Scholar PubMed

273. Fiume L, Manerba M, Vettraino M, Di Stefano G. Inhibition of lactate dehydrogenase activity as an approach to cancer therapy. Future Med Chem 2014;6:429–45.10.4155/fmc.13.206Suche in Google Scholar PubMed

274. Le A, Cooper CR, Gouw AM, Dinavahi R, Maitra A, Deck LM, Royer RE, Vander Jagt DL, Semenza GL, Dang CV. Inhibition of lactate dehydrogenase A induces oxidative stress and inhibits tumor progression. Proc Natl Acad Sci USA 2010;107:2037–42.10.1073/pnas.0914433107Suche in Google Scholar PubMed PubMed Central

275. Xie H, Hanai J, Ren JG, Kats L, Burgess K, Bhargava P, Signoretti S, Billiard J, Duffy KJ, Grant A, Wang X, Lorkiewicz PK, Schatzman S, Bousamra M 2nd, Lane AN, Higashi RM, Fan TW, Pandolfi PP, Sukhatme VP, Seth P. Targeting lactate dehydrogenase – a inhibits tumorigenesis and tumor progression in mouse models of lung cancer and impacts tumor-initiating cells. Cell Metab 2014;19:795–809.10.1016/j.cmet.2014.03.003Suche in Google Scholar PubMed PubMed Central

276. Yang Y, Su D, Zhao L, Zhang D, Xu J, Wan J, Fan S, Chen M. Different effects of LDH-A inhibition by oxamate in non-small cell lung cancer cells. Oncotarget 2014;5:11886–96.10.18632/oncotarget.2620Suche in Google Scholar PubMed PubMed Central

277. Xie H, Valera VA, Merino MJ, Amato AM, Signoretti S, Linehan WM, Sukhatme VP, Seth P. LDH-A inhibition, a therapeutic strategy for treatment of hereditary leiomyomatosis and renal cell cancer. Mol Cancer Ther 2009;8:626–35.10.1158/1535-7163.MCT-08-1049Suche in Google Scholar PubMed PubMed Central

278. Wang ZY, Loo TY, Shen JG, Wang N, Wang DM, Yang DP, Mo SL, Guan XY, Chen JP. LDH-A silencing suppresses breast cancer tumorigenicity through induction of oxidative stress mediated mitochondrial pathway apoptosis. Breast Cancer Res Treat 2012;131:791–800.10.1007/s10549-011-1466-6Suche in Google Scholar PubMed

279. Fiume L, Manerba M, Vettraino M, Di Stefano G. Impairment of aerobic glycolysis by inhibitors of lactic dehydrogenase hinders the growth of human hepatocellular carcinoma cell lines. Pharmacology 2010;86:157–62.10.1159/000317519Suche in Google Scholar PubMed

280. Sheng SL, Liu JJ, Dai YH, Sun XG, Xiong XP, Huang G. Knockdown of lactate dehydrogenase A suppresses tumor growth and metastasis of human hepatocellular carcinoma. FEBS J 2012;279:3898–910.10.1111/j.1742-4658.2012.08748.xSuche in Google Scholar PubMed

281. Zhai X, Yang Y, Wan J, Zhu R, Wu Y. Inhibition of LDH-A by oxamate induces G2/M arrest, apoptosis and increases radiosensitivity in nasopharyngeal carcinoma cells. Oncol Rep 2013;30:2983–91.10.3892/or.2013.2735Suche in Google Scholar PubMed

282. Maftouh M, Avan A, Sciarrillo R, Granchi C, Leon LG, Rani R, Funel N, Smid K, Honeywell R, Boggi U, Minutolo F, Peters GJ, Giovannetti E. Synergistic interaction of novel lactate dehydrogenase inhibitors with gemcitabine against pancreatic cancer cells in hypoxia. Br J Cancer 2014;110:172–82.10.1038/bjc.2013.681Suche in Google Scholar PubMed PubMed Central

283. Price GS, Page RL, Riviere JE, Cline JM, Thrall DE. Pharmacokinetics and toxicity of oral and intravenous lonidamine in dogs. Cancer Chemother Pharmacol 1996;38:129–35.10.1007/s002800050460Suche in Google Scholar PubMed

284. Gatzemeier U, Cavalli F, Häussinger K, Kaukel E, Koschel G, Martinelli G, Neuhauss R, von Pawel J. Phase III trial with and without lonidamine in non-small cell lung cancer. Semin Oncol 1991;18(2 Suppl):42–8.Suche in Google Scholar

285. Wang K, Fan H, Chen Q, Ma G, Zhu M, Zhang X, Zhang Y, Yu J. Curcumin inhibits aerobic glycolysis and induces mitochondrial-mediated apoptosis through hexokinase II in human colorectal cancer cells in vitro. Anticancer Drugs 2015;26:15–24.10.1097/CAD.0000000000000132Suche in Google Scholar PubMed

286. Liu Z, Zhang Y-Y, Zhang Q-W, Zhao S-R, Wu C-Z, Cheng X, Jiang C-C, Jiang Z-W, Liu H. 3-Bromopyruvate induces apoptosis in breast cancer cells by downregulating Mcl-1 through the PI3K/Akt signaling pathway. Anticancer Drugs 2014;25:447–55.10.1097/CAD.0000000000000081Suche in Google Scholar PubMed

287. Ganapathy-Kanniappan S, Geschwind J-F, Kunjithapatham R, Buijs M, Vossen JA, Tchernyshyov I, Cole RN, Syed LH, Rao PP, Ota S, Vali M. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is pyruvylated during 3-bromopyruvate mediated cancer cell death. Anticancer Res 2009;29:4909–18.Suche in Google Scholar

288. Ihrlund LS, Hernlund E, Khan O, Shoshan MC. 3-Bromopyruvate as inhibitor of tumour cell energy metabolism and chemopotentiator of platinum drugs. Mol Oncol 2008;2:94–101.10.1016/j.molonc.2008.01.003Suche in Google Scholar PubMed PubMed Central

289. Zhao Y, Butler EB, Tan M. Targeting cellular metabolism to improve cancer therapeutics. Cell Death Dis 2013;4:e532.10.1038/cddis.2013.60Suche in Google Scholar PubMed PubMed Central

290. Chapiro J, Sur S, Savic LJ, Ganapathy-Kanniappan S, Reyes J, Duran R, Thiruganasambandam SC, Moats CR, Lin M, Luo W, Tran PT, Herman JM, Semenza GL, Ewald AJ, Vogelstein B, Geschwind JF. Systemic delivery of microencapsulated 3-bromopyruvate for the therapy of pancreatic cancer. Clin Cancer Res 2014;20:6406–17.10.1158/1078-0432.CCR-14-1271Suche in Google Scholar PubMed PubMed Central

291. Ganapathy-Kanniappan S, Vali M, Kunjithapatham R, Buijs M, Syed LH, Rao PP, Ota S, Kwak BK, Loffroy R, Geschwind JF. 3-Bromopyruvate: a new targeted antiglycolytic agent and a promise for cancer therapy. Curr Pharm Biotechnol 2010;11:510–7.10.2174/138920110791591427Suche in Google Scholar PubMed

292. Klarer AC, O’Neal J, Imbert-Fernandez Y, Clem A, Ellis SR, Clark J, Clem B, Chesney J, Telang S. Inhibition of 6-phosphofructo-2-kinase (PFKFB3) induces autophagy as a survival mechanism. Cancer Metab 2014;1:2.10.1186/2049-3002-2-2Suche in Google Scholar PubMed PubMed Central

293. Clem BF, O’Neal J, Tapolsky G, Clem AL, Imbert-Fernandez Y, Kerr DA 2nd, Klarer AC, Redman R, Miller DM, Trent JO, Telang S, Chesney J. Targeting 6-phosphofructo-2-kinase (PFKFB3) as a therapeutic strategy against cancer. Mol Cancer Ther 2013;12:1461–70.10.1158/1535-7163.MCT-13-0097Suche in Google Scholar PubMed PubMed Central

294. Pinheiro C, Longatto-Filho A, Azevedo-Silva J, Casal M, Schmitt FC, Baltazar F. Role of monocarboxylate transporters in human cancers: state of the art. J Bioenerg Biomembr 2012;44:127–39.10.1007/s10863-012-9428-1Suche in Google Scholar PubMed

295. Cancer Research UK. ClinicalTrials.gov [Internet] Bethesda (MD): National Library of Medicine (US). A Phase I Trial of AZD3965 in Patients With Advanced Cancer. 2013 [cited 2014 Dec 20]. Available from: https://clinicaltrials.gov/ct2/show/NCT01791595. NLM identifier: NCT01791595.Suche in Google Scholar

296. Doherty JR, Yang C, Scott KE, Cameron MD, Fallahi M, Li W, Hall MA, Amelio AL, Mishra JK, Li F, Tortosa M, Genau HM, Rounbehler RJ, Lu Y, Dang CV, Kumar KG, Butler AA, Bannister TD, Hooper AT, Unsal-Kacmaz K, Roush WR, Cleveland JL. Blocking lactate export by inhibiting the Myc target MCT1 Disables glycolysis and glutathione synthesis. Cancer Res 2014;74:908–20.10.1158/0008-5472.CAN-13-2034Suche in Google Scholar PubMed PubMed Central

297. Curry JM, Tuluc M, Whitaker-Menezes D, Ames JA, Anantharaman A, Butera A, Leiby B, Cognetti DM, Sotgia F, Lisanti MP, Martinez-Outschoorn UE. Cancer metabolism, stemness and tumor recurrence: MCT1 and MCT4 are functional biomarkers of metabolic symbiosis in head and neck cancer. Cell Cycle 2013;12:1371–84.10.4161/cc.24092Suche in Google Scholar PubMed PubMed Central

298. Liu Y, Cao Y, Zhang W, Bergmeier S, Qian Y, Akbar H, Colvin R, Ding J, Tong L, Wu S, Hines J, Chen X. A small-molecule inhibitor of glucose transporter 1 downregulates glycolysis, induces cell-cycle arrest, and inhibits cancer cell growth in vitro and in vivo. Mol Cancer Ther 2012;11:1672–82.10.1158/1535-7163.MCT-12-0131Suche in Google Scholar PubMed

299. Ryland LK, Doshi UA, Shanmugavelandy SS, Fox TE, Aliaga C, Broeg K, Baab KT, Young M, Khan O, Haakenson JK, Jarbadan NR, Liao J, Wang H-G, Feith DJ, Loughran Jr TP, Liu X, Kester M. C6-ceramide nanoliposomes target the Warburg effect in chronic lymphocytic leukemia. PLoS One 2013;8:e84648.10.1371/journal.pone.0084648Suche in Google Scholar PubMed PubMed Central

300. Wiench B, Eichhorn T, Paulsen M, Efferth T. Shikonin directly targets mitochondria and causes mitochondrial dysfunction in cancer cells. eCAM 2012;2012:726025.10.1155/2012/726025Suche in Google Scholar PubMed PubMed Central

301. Omidi Y, Matthaiou E, Barar J, Coukos G, Sandaltzopoulos R, Li C. Shikonin-loaded antibody-armed nanoparticles for targeted therapy of ovarian cancer. Int J Nanomedicine 2014;15:1855–70.10.2147/IJN.S51880Suche in Google Scholar PubMed PubMed Central

302. Chen J, Xie J, Jiang Z, Wang B, Wang Y, Hu X. Shikonin and its analogs inhibit cancer cell glycolysis by targeting tumor pyruvate kinase-M2. Oncogene 2011;30:4297–306.10.1038/onc.2011.137Suche in Google Scholar PubMed

303. Shi S, Cao H. Shikonin promotes autophagy in BXPC-3 human pancreatic cancer cells through the PI3K/Akt signaling pathway. Oncology Lett 2014;8:1087–9.10.3892/ol.2014.2293Suche in Google Scholar PubMed PubMed Central

304. Wymann MP, Bulgarelli-Leva G, Zvelebil MJ, Pirola L, Vanhaesebroeck B, Waterfield MD, Panayotou G. Wortmannin inactivates phosphoinositide 3-kinase by covalent modification of Lys-802, a residue involved in the phosphate transfer reaction. Mol Cell Biol 1996;16:1722–33.10.1128/MCB.16.4.1722Suche in Google Scholar PubMed PubMed Central

305. Beckner ME, Gobbel GT, Abounader R, Burovic F, Agostino NR, Laterra J, Pollack IF. Glycolytic glioma cells with active glycogen synthase are sensitive to PTEN and inhibitors of PI3K and gluconeogenesis. Lab Invest 2005;85:1457–70.10.1038/labinvest.3700355Suche in Google Scholar PubMed

306. Levy B, Spira A, Becker D, Evans T, Schnadig I, Camidge DR, Bauman JE, Hausman D, Walker L, Nemunaitis J, Rudin CM, Halmos B, Bowles DW. A randomized, phase 2 trial of Docetaxel with or without PX-866, an irreversible oral phosphatidylinositol 3-kinase inhibitor, in patients with relapsed or metastatic non-small-cell lung cancer. J Thorac Oncol 2014;9:1031–5.10.1097/JTO.0000000000000183Suche in Google Scholar PubMed

307. Ihle NT, Paine-Murrieta G, Berggren MI, Baker A, Tate WR, Wipf P, Abraham RT, Kirkpatrick DL, Powis G. The phosphatidylinositol-3-kinase inhibitor PX-866 overcomes resistance to the epidermal growth factor receptor inhibitor gefitinib in A-549 human non-small cell lung cancer xenografts. Mol Cancer Ther 2005;4:1349–57.10.1158/1535-7163.MCT-05-0149Suche in Google Scholar PubMed PubMed Central

308. Koul D, Shen R, Kim YW, Kondo Y, Lu Y, Bankson J, Ronen SM, Kirkpatrick DL, Powis G, Yung WK. Cellular and in vivo activity of a novel PI3K inhibitor, PX-866, against human glioblastoma. Neuro Oncol 2010;12:559–69.10.1093/neuonc/nop058Suche in Google Scholar PubMed PubMed Central

309. Bowles DW, Ma WW, Senzer N, Brahmer JR, Adjei AA, Davies M, Lazar AJ, Vo A, Peterson S, Walker L, Hausman D, Rudin CM, Jimeno A. A multicenter phase 1 study of PX-866 in combination with docetaxel in patients with advanced solid tumours. Br J Cancer 2013;109:1085–92.10.1038/bjc.2013.474Suche in Google Scholar PubMed PubMed Central

310. Hong DS, Bowles DW, Falchook GS, Messersmith WA, George GC, O’Bryant CL, Vo AC, Klucher K, Herbst RS, Eckhardt SG, Peterson S, Hausman DF, Kurzrock R, Jimeno A. A multicenter phase I trial of PX-866, an oral irreversible phosphatidylinositol 3-kinase inhibitor, in patients with advanced solid tumors. Clin Cancer Res 2012;18:4173–82.10.1158/1078-0432.CCR-12-0714Suche in Google Scholar PubMed

311. Bowles DW, Senzer N, Hausman D, Peterson S, Vo A, Walker L, Cohen RB, Jimeno A. A multicenter phase 1 study of PX-866 and cetuximab in patients with metastatic colorectal carcinoma or recurrent/metastatic squamous cell carcinoma of the head and neck. Invest New Drugs 2014;32:1197–203.10.1007/s10637-014-0124-3Suche in Google Scholar PubMed

312. Marone R, Cmiljanovic V, Giese B, Wymann MP. Targeting phosphoinositide 3-kinase: moving towards therapy. Biochim Biophys Acta 2008;1784:159–85.10.1016/j.bbapap.2007.10.003Suche in Google Scholar PubMed

313. Knight ZA, Shokat KM. Chemically targeting the PI3K family. Biochem Soc Trans 2007;35:245–9.10.1042/BST0350245Suche in Google Scholar PubMed

314. FDA approves first PI3K inhibitor. Nat Rev Drug Discov 2014;13:644–5. Available at: http://www.nature.com/nrd/journal/v13/n9/full/nrd4425.html.10.1038/nrd4425Suche in Google Scholar

315. Tili E, Michaille J-J, Luo Z, Volinia S, Rassenti LZ, Kipps TJ, Croce CM. The down-regulation of miR-125b in chronic lymphocytic leukemias leads to metabolic adaptation of cells to a transformed state. Blood 2012;120:2631–8.10.1182/blood-2012-03-415737Suche in Google Scholar PubMed PubMed Central

316. Martinez Marignac VL, Smith S, Toban N, Bazile M, Aloyz R. Resistance to Dasatinib in primary chronic lymphocytic leukemia lymphocytes involves AMPK-mediated energetic re-programming. Oncotarget 2013;4:2550–66.10.18632/oncotarget.1508Suche in Google Scholar PubMed PubMed Central

317. Furman RR, Sharman JP, Coutre SE, Cheson BD, Pagel JM, Hillmen P, Barrientos JC, Zelenetz AD, Kipps TJ, Flinn I, Ghia P, Eradat H, Ervin T, Lamanna N, Coiffier B, Pettitt AR, Ma S, Stilgenbauer S, Cramer P, Aiello M, Johnson DM, Miller LL, Li D, Jahn TM, Dansey RD, Hallek M, O’Brien SM. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. New Engl J Med 2014;370:997–1007.10.1056/NEJMoa1315226Suche in Google Scholar PubMed PubMed Central

318. Dang CV. MYC, Metabolism, cell growth, and tumorigenesis. Cold Spring Harbor Persp Med 2013;3:a014217-a.10.1101/cshperspect.a014217Suche in Google Scholar PubMed PubMed Central

319. Shaw RJ, Cantley LC. Ras, PI(3)K and mTOR signalling controls tumour cell growth. Nature 2006;441:424–30.10.1038/nature04869Suche in Google Scholar PubMed

320. Gera JF. AKT activity determines sensitivity to mammalian target of rapamycin (mTOR) inhibitors by regulating cyclin D1 and c-myc expression. J Biol Chem 2003;279:2737–46.10.1074/jbc.M309999200Suche in Google Scholar PubMed

321. Shimobayashi M, Hall MN. Making new contacts: the mTOR network in metabolism and signalling crosstalk. Nat Rev Mol Cell Biol 2014;15:155–62.10.1038/nrm3757Suche in Google Scholar PubMed

322. Düvel K, Yecies JL, Menon S, Raman P, Lipovsky AI, Souza AL, Triantafellow E, Ma Q, Gorski R, Cleaver S, Vander Heiden MG, MacKeigan JP, Finan PM, Clish CB, Murphy LO, Manning BD. Activation of a metabolic gene regulatory network downstream of mTOR complex 1. Mol Cell 2010;39:171–83.10.1016/j.molcel.2010.06.022Suche in Google Scholar PubMed PubMed Central

323. Ben-Sahra I, Howell JJ, Asara JM, Manning BD. Stimulation of de novo pyrimidine synthesis by growth signaling through mTOR and S6K1. Science 2013;339:1323–8.10.1126/science.1228792Suche in Google Scholar PubMed PubMed Central

324. Edinger AL, Linardic CM, Chiang GG, Thompson CB, Abraham RT. Differential effects of rapamycin on mammalian target of rapamycin signaling functions in mammalian cells. Cancer Res 2003;63:8451–60.Suche in Google Scholar

325. Peng T, Golub TR, Sabatini DM. The immunosuppressant rapamycin mimics a starvation-like signal distinct from amino acid and glucose deprivation. Mol Cell Biol 2002;22:5575–84.10.1128/MCB.22.15.5575-5584.2002Suche in Google Scholar PubMed PubMed Central

326. Pang Y-Y, Wang T, Chen F-Y, Wu Y-L, Shao X, Xiao F, Huang H-H, Zhong H, Zhong J-H. Glycolytic inhibitor 2-deoxy-d-glucose suppresses cell proliferation and enhances methylprednisolone sensitivity in non-Hodgkin lymphoma cells through down-regulation of HIF-1α and c-MYC. Leuk Lymphoma 2014;1–10. DOI: 10.3109/10428194.2014.963575.10.3109/10428194.2014.963575Suche in Google Scholar PubMed

327. Gottfried E, Lang SA, Renner K, Bosserhoff A, Gronwald W, Rehli M, Einhell S, Gedig I, Singer K, Seilbeck A, Mackensen A, Grauer O, Hau P, Dettmer K, Andreesen R, Oefner PJ, Kreutz M. New Aspects of an old drug – diclofenac targets MYC and glucose metabolism in tumor cells. PLoS One 2013;8:e66987.10.1371/journal.pone.0066987Suche in Google Scholar PubMed PubMed Central

328. Hoferová Z, Fedorocko P, Hofmanová J, Hofer M, Znojil V, Minksová K, Soucek K, Egyed A, Kozubík A. The effect of nonsteroidal antiinflammatory drugs ibuprofen, flurbiprofen, and diclofenac on in vitro and in vivo growth of mouse fibrosarcoma. Cancer Invest 2002;20:490–8.10.1081/CNV-120002149Suche in Google Scholar

329. Mayorek N, Naftali-Shani N, Grunewald M. Diclofenac inhibits tumor growth in a murine model of pancreatic cancer by modulation of VEGF levels and arginase activity. PLoS One 2010;5:e12715.10.1371/journal.pone.0012715Suche in Google Scholar PubMed PubMed Central

330. Advanced Cancer Therapeutics. ClinicalTrials.gov [Internet] Bethesda (MD): National Library of Medicine (US). Phase 1 Safety Study of ACT-PFK-158, 2HCL in Patients with Advanced Solid Malignancies. 2014 [cited 2014 Dec 20]. Available from: https://clinicaltrials.gov/ct2/show/NCT02044861. NLM identifier: NCT02044861.Suche in Google Scholar

331. University of Chicago. ClinicalTrials.gov [Internet] Bethesda (MD): National Library of Medicine (US). Lenalidomide and Combination Chemotherapy (DA-EPOCH-R) in Treating Patients With MYC-Associated B-Cell Lymphomas. 2014 [cited 2014 Dec 20]. Available from: https://clinicaltrials.gov/ct2/show/NCT02213913. NLM identifier: NCT02213913.Suche in Google Scholar

332. Boston VA Research Institute. ClinicalTrials.gov [Internet] Bethesda (MD): National Library of Medicine (US). Study to Evaluate Two Lenalidomide Dose Regimens With Low Dose Dexamethasone for the Treatment Relapsed Multiple Myeloma. 2013 [cited 2014 Dec 20]. Available from: https://clinicaltrials.gov/ct2/show/NCT01380106. NLM identifier: NCT01380106.Suche in Google Scholar

333. Kristie Blum. ClinicalTrials.gov [Internet] Bethesda (MD): National Library of Medicine (US). A Phase II Trial of Panobinostat and Lenalidomide in Patients With Relapsed or Refractory Hodgkin’s Lymphoma. 2013 [cited 2013 Dec 20]. Available from: https://clinicaltrials.gov/ct2/show/NCT01460940. NLM identifier: NCT01460940.Suche in Google Scholar

334. Chang DT. Stanford University. ClinicalTrials.gov [Internet] Bethesda (MD): National Library of Medicine (US). Phase I Trial of Metabolic Reprogramming Therapy for Treatment of Recurrent Head and Neck Cancers. 2014 [cited 2014 Dec 20]. Available from: https://clinicaltrials.gov/ct2/show/NCT01163487. NLM identifier: NCT01163487.Suche in Google Scholar

335. Sheba Medical Center. ClinicalTrials.gov [Internet] Bethesda (MD): National Library of Medicine (US). Phase II Study of RAD001 in a Neoadjuvant Setting in Men With Intermediate or High Risk Prostate Cancer. 2009 [cited 2014 Dec 20]. Available from: https://clinicaltrials.gov/ct2/show/NCT00657982. NLM identifier: NCT00657982.Suche in Google Scholar

336. National Cancer Center, Korea. ClinicalTrials.gov [Internet] Bethesda (MD): National Library of Medicine (US). Phase Ib/II Trials of RAD001 in Triple Negative Metastatic Breast Cancer. 2014 [cited 2014 Dec 20]. Available from: https://clinicaltrials.gov/ct2/show/NCT01939418. NLM identifier: NCT01939418.Suche in Google Scholar

337. University of California, San Francisco. ClinicalTrials.gov [Internet] Bethesda (MD): National Library of Medicine (US). Phase II Trial of RAD001 in Patients With Recurrent Low Grade Glioma. 2014 [cited 2014 Dec 20]. Available from: https://clinicaltrials.gov/ct2/show/NCT00823459. NLM identifier: NCT00823459.Suche in Google Scholar

338. Chinese University of Hong Kong. ClinicalTrials.gov [Internet] Bethesda (MD): National Library of Medicine (US). Gastric Cancer RAD001 Study. 2014 [cited 2014 Dec 20]. Available from: https://clinicaltrials.gov/ct2/show/NCT01514110. NLM identifier: NCT01514110.Suche in Google Scholar

339. Ohio State University Comprehensive Cancer Center. ClinicalTrials.gov [Internet] Bethesda (MD): National Library of Medicine (US). Pilot Study of Curcumin for Women With Obesity and High Risk for Breast Cancer. 2014 [cited 2014 Dec 20]. Available from: https://clinicaltrials.gov/ct2/show/NCT01975363. NLM identifier: NCT01975363.Suche in Google Scholar

340. Shahid Beheshtu Medical University. ClinicalTrials.gov [Internet] Bethesda (MD): National Library of Medicine (US). Radiosensitizing and Radioprotectve Effects of Curcumin in Prostate Cancer. 2013 [cited 2014 Dec 20]. Available from: https://clinicaltrials.gov/ct2/show/NCT01917890. NLM identifier: NCT01917890.Suche in Google Scholar

341. Case Comprehensive Cancer Center. ClinicalTrials.gov [Internet] Bethesda (MD): National Library of Medicine (US). Curcumin and Cholecalciferol in Treating Patients With Previously Untreated Stage 0-II Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma. 2014 [cited 2014 Dec 20]. Available from: https://clinicaltrials.gov/ct2/show/NCT02100423. NLM identifier: NCT02100423.Suche in Google Scholar

342. Genentech, Inc. ClinicalTrials.gov [Internet] Bethesda (MD): National Library of Medicine (US). Study of GDC-0941 or GDC-0980 With Fulvestrant Versus Fulvestrant in Advanced or Metastatic Breast Cancer in Patients Resistant to Aromatase Inhibitor Therapy. 2014 [cited 2014 Dec 20]. Available from: https://clinicaltrials.gov/ct2/show/NCT01437566. NLM identifier: NCT01437566.Suche in Google Scholar

343. Roswell Park Cancer Institute. ClinicalTrials.gov [Internet] Bethesda (MD): National Library of Medicine (US). PI3K Inhibitor BKM120 and Docetaxel in Treating Patients With Advanced Solid Tumor That is Locally Advanced, Cannot Be Removed By Surgery, or Metastatic. 344. PI3K Inhibitor BKM120 and Cetuximab in Treating Patients With Recurrent or Metastatic Head and Neck Cancer. 2014 [cited 2014 Dec 20]. Available from: https://clinicaltrials.gov/ct2/show/NCT01540253. NLM indetifier: NCT01540253.Suche in Google Scholar

344. University of Chicago. ClinicalTrials.gov [Internet] Bethesda (MD): National Library of Medicine (US). PI3K Inhibitor BKM120 and Cetuximab in Treating Patients With Recurrent or Metastatic Head and Neck Cancer. 2014 [cited 2014 Dec 20]. Available from: https://clinicaltrials.gov/ct2/show/NCT01816984. NLM identifier: NCT01816984.Suche in Google Scholar

345. Novartus Pharmaceuticals. ClinicalTrials.gov [Internet] Bethesda (MD): National Library of Medicine (US). A Study of Oral LGK974 in Patients With Malignancies Dependent on Wnt Ligands. 2014 [cited 2014 Dec 20]. Available from: https://clinicaltrials.gov/ct2/show/NCT01351103. NLM identifier: NCT01351103.Suche in Google Scholar

346. JW Pharmaceutical. ClinicalTrials.gov [Internet] Bethesda (MD): National Library of Medicine (US). Phase I Clinical Study of CWP232291 in Acute Myeloid Leukemia Patients. 2014 [cited 2014 Dec 20]. Available from: https://clinicaltrials.gov/ct2/show/NCT01398462. NLM identifier: NCT01398462.Suche in Google Scholar

347. Prism Pharma Co, Ltd. ClinicalTrials.gov [Internet] Bethesda (MD): National Library of Medicine (US). Safety and Efficacy Study of PRI-724 in Subjects With Advanced Myeloid Malignancies. 2014 [cited 2014 Dec 20]. Available from: https://clinicaltrials.gov/ct2/show/NCT01606579. NLM identifier: NCT01606579.Suche in Google Scholar

348. Philogen S.p.A. ClinicalTrials.gov [Internet] Bethesda (MD): National Library of Medicine (US). L19TNFα in Combination With Doxorubicin in Patients With Advanced Solid Tumours. 2014 [cited 2014 Dec 20]. Available from: https://clinicaltrials.gov/ct2/show/NCT02076620. NLM identifier: NCT02076620.Suche in Google Scholar

349. Sidney Kimmel Comprehensive Cancer Center. ClinicalTrials.gov [Internet] Bethesda (MD): National Library of Medicine (US). DIG-HIF1 Pharmacodynamic Trial in Newly Diagnosed Operable Breast Cancer. 2014 [cited 2014 Dec 20]. Available from: https://clinicaltrials.gov/ct2/show/NCT01763931. NLM identifier: NCT01763931.Suche in Google Scholar

350. National Cancer Institute (NCI). ClinicalTrials.gov [Internet] Bethesda (MD): National Library of Medicine (US). Ganetespib and Ziv-Aflibercept in Refractory Gastrointestinal Carcinomas, Non-Squamous Non-Small Cell Lung Carcinomas, Urothelial Carcinomas, and Sarcomas. 2014 [cited 2014 Dec 20]. Available from: https://clinicaltrials.gov/ct2/show/NCT02192541. NLM identifier: NCT02192541.Suche in Google Scholar

351. Massachusetts General Hospital. ClinicalTrials.gov [Internet] Bethesda (MD): National Library of Medicine (US). CRLX101 in Combination With Bevacizumab for Recurrent Ovarian/Tubal/Peritoneal Cancer. 2014 [cited 2014 Dec 20]. Available from: https://clinicaltrials.gov/ct2/show/NCT01652079. NLM identifier: NCT01652079.Suche in Google Scholar

352. OHSU Knight Cancer Institute. ClinicalTrials.gov [Internet] Bethesda (MD): National Library of Medicine (US). Phenelzine Sulfate and Docetaxel in Treating Patients With Prostate Cancer With Progressive Disease After First-Line Therapy With Docetaxel. 2014 [cited 2014 Dec 20]. Available from: https://clinicaltrials.gov/ct2/show/NCT01253642. NLM identifier: NCT01253642.Suche in Google Scholar