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The miRNA-kallikrein interaction: a mosaic of epigenetic regulation in cancer

  • Ashley Di Meo , Cong Wang , Yufeng Cheng , Eleftherios P. Diamandis and George M. Yousef EMAIL logo
Published/Copyright: March 31, 2018

Abstract

The kallikrein-related peptidases (KLKs) constitute a family of 15 highly conserved serine proteases with trypsin- and chymotrypsin-like activities. Dysregulated expression and/or aberrant activation of KLKs has been linked to various pathophysiological processes, including cancer. Many KLKs have been identified as potential cancer biomarkers. microRNAs (miRNAs) are a class of small non-coding RNAs that regulate gene expression by pairing to the 3′ untranslated region (UTR) of complimentary mRNA targets. miRNAs are dysregulated in many cancers, including prostate, kidney and ovarian cancers. Several studies have shown that miRNAs are involved in the post-transcriptional regulation of KLKs. However, recent evidence suggests that miRNAs can also act as downstream effectors of KLKs. In this review, we provide an update on the epigenetic regulation of KLKs by miRNAs. We also present recent experimental evidence that supports the regulatory role of KLKs on miRNA networks. The potential diagnostic and therapeutic applications of miRNA-kallikrein interactions are also discussed.

References

Ahmed, N., Dorn, J., Napieralski, R., Drecoll, E., Kotzsch, M., Goettig, P., Zein, E., Avril, S., Kiechle, M., Diamandis, E.P., et al. (2016). Clinical relevance of kallikrein-related peptidase 6 (KLK6) and 8 (KLK8) mRNA expression in advanced serous ovarian cancer. Biol. Chem. 397, 1265–1276.10.1515/hsz-2016-0177Search in Google Scholar PubMed PubMed Central

Al Olama, A.A., Kote-Jarai, Z., Berndt, S.I., Conti, D.V., Schumacher, F., Han, Y., Benlloch, S., Hazelett, D.J., Wang, Z., Saunders, E., et al. (2014). A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer. Nat. Genet. 46, 1103–1109.10.1038/ng.3094Search in Google Scholar PubMed PubMed Central

Anastasiadou, E., Jacob, L.S., and Slack, F.J. (2018). Non-coding RNA networks in cancer. Nat. Rev. Cancer 18, 5–18.10.1038/nrc.2017.99Search in Google Scholar PubMed PubMed Central

Avgeris, M. and Scorilas, A. (2016). Kallikrein-related peptidases (KLKs) as emerging therapeutic targets: focus on prostate cancer and skin pathologies. Expert Opin. Ther. Targets 20, 801–818.10.1517/14728222.2016.1147560Search in Google Scholar PubMed

Avgeris, M., Stravodimos, K., and Scorilas, A. (2014). Loss of miR-378 in prostate cancer, a common regulator of KLK2 and KLK4, correlates with aggressive disease phenotype and predicts the short-term relapse of the patients. Biol. Chem. 395, 1095–1104.10.1515/hsz-2014-0150Search in Google Scholar PubMed

Bayani, J., Kuzmanov, U., Saraon, P., Fung, W.A., Soosaipillai, A., Squire, J.A., and Diamandis, E.P. (2013). Copy number and expression alterations of miRNAs in the ovarian cancer cell line OVCAR-3: impact on kallikrein 6 protein expression. Clin. Chem. 59, 296–305.10.1373/clinchem.2012.193060Search in Google Scholar PubMed

Bayat Mokhtari, R., Homayouni, T.S., Baluch, N., Morgatskaya, E., Kumar, S., Das, B., and Yeger, H. (2017). Combination therapy in combating cancer. Oncotarget 8, 38022–38043.10.18632/oncotarget.16723Search in Google Scholar PubMed PubMed Central

Borgono, C.A., Michael, I.P., and Diamandis, E.P. (2004). Human tissue kallikreins: physiologic roles and applications in cancer. Mol. Cancer Res. 2, 257–280.10.1158/1541-7786.257.2.5Search in Google Scholar

Borrebaeck, C.A. (2017). Precision diagnostics: moving towards protein biomarker signatures of clinical utility in cancer. Nat. Rev. Cancer 17, 199–204.10.1038/nrc.2016.153Search in Google Scholar PubMed

Bracken, C.P., Scott, H.S., and Goodall, G.J. (2016). A network-biology perspective of microRNA function and dysfunction in cancer. Nat. Rev. Genet. 17, 719–732.10.1038/nrg.2016.134Search in Google Scholar PubMed

Butz, H., Szabo, P.M., Nofech-Mozes, R., Rotondo, F., Kovacs, K., Mirham, L., Girgis, H., Boles, D., Patocs, A., and Yousef, G.M. (2014). Integrative bioinformatics analysis reveals new prognostic biomarkers of clear cell renal cell carcinoma. Clin. Chem. 60, 1314–1326.10.1373/clinchem.2014.225854Search in Google Scholar PubMed

Butz, H., Szabo, P.M., Khella, H.W., Nofech-Mozes, R., Patocs, A., and Yousef, G.M. (2015). miRNA-target network reveals miR-124as a key miRNA contributing to clear cell renal cell carcinoma aggressive behaviour by targeting CAV1 and FLOT1. Oncotarget 6, 12543–12557.10.18632/oncotarget.3815Search in Google Scholar PubMed PubMed Central

Calin, G.A. and Croce, C.M. (2006). MicroRNAs and chromosomal abnormalities in cancer cells. Oncogene 25, 6202–6210.10.1038/sj.onc.1209910Search in Google Scholar PubMed

Calin, G.A., Sevignani, C., Dumitru, C.D., Hyslop, T., Noch, E., Yendamuri, S., Shimizu, M., Rattan, S., Bullrich, F., Negrini, M., et al. (2004). Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc. Natl. Acad. Sci. USA 101, 2999–3004.10.1073/pnas.0307323101Search in Google Scholar PubMed PubMed Central

Chow, T.F., Crow, M., Earle, T., El-Said, H., Diamandis, E.P., and Yousef, G.M. (2008). Kallikreins as microRNA targets: an in silico and experimental-based analysis. Biol. Chem. 389, 731–738.10.1515/BC.2008.071Search in Google Scholar PubMed

Chu, H., Zhong, D., Tang, J., Li, J., Xue, Y., Tong, N., Qin, C., Yin, C., Zhang, Z., and Wang, M. (2016). A functional variant in miR-143 promoter contributes to prostate cancer risk. Arch. Toxicol. 90, 403–414.10.1007/s00204-014-1396-2Search in Google Scholar PubMed

Cook, N., Hansen, A.R., Siu, L.L., and Abdul Razak, A.R. (2015). Early phase clinical trials to identify optimal dosing and safety. Mol. Oncol. 9, 997–1007.10.1016/j.molonc.2014.07.025Search in Google Scholar PubMed PubMed Central

Cyll, K., Ersvaer, E., Vlatkovic, L., Pradhan, M., Kildal, W., Avranden Kjaer, M., Kleppe, A., Hveem, T.S., Carlsen, B., Gill, S., et al. (2017). Tumour heterogeneity poses a significant challenge to cancer biomarker research. Br. J. Cancer 117, 367–375.10.1038/bjc.2017.171Search in Google Scholar PubMed PubMed Central

Di Meo, A., Bartlett, J., Cheng, Y., Pasic, M.D., and Yousef, G.M. (2017). Liquid biopsy: a step forward towards precision medicine in urologic malignancies. Mol. Cancer 16, 80.10.1186/s12943-017-0644-5Search in Google Scholar PubMed PubMed Central

Diamandis, E.P. and Yousef, G.M. (2002). Human tissue kallikreins: a family of new cancer biomarkers. Clin. Chem. 48, 1198–1205.10.1093/clinchem/48.8.1198Search in Google Scholar

Eeles, R.A., Olama, A.A., Benlloch, S., Saunders, E.J., Leongamornlert, D.A., Tymrakiewicz, M., Ghoussaini, M., Luccarini, C., Dennis, J., Jugurnauth-Little, S., et al. (2013). Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array. Nat. Genet. 45, 385–391.10.1038/ng.2560Search in Google Scholar PubMed PubMed Central

Grimson, A., Farh, K.K., Johnston, W.K., Garrett-Engele, P., Lim, L.P., and Bartel, D.P. (2007). MicroRNA targeting specificity in mammals: determinants beyond seed pairing. Mol. Cell 27, 91–105.10.1016/j.molcel.2007.06.017Search in Google Scholar PubMed PubMed Central

Gulati, S., Martinez, P., Joshi, T., Birkbak, N.J., Santos, C.R., Rowan, A.J., Pickering, L., Gore, M., Larkin, J., Szallasi, Z., et al. (2014). Systematic evaluation of the prognostic impact and intratumour heterogeneity of clear cell renal cell carcinoma biomarkers. Eur. Urol. 66, 936–948.10.1016/j.eururo.2014.06.053Search in Google Scholar PubMed PubMed Central

Hanash, S.M., Pitteri, S.J., and Faca, V.M. (2008). Mining the plasma proteome for cancer biomarkers. Nature 452, 571–579.10.1038/nature06916Search in Google Scholar PubMed

Jimenez, L., Sharma, V.P., Condeelis, J., Harris, T., Ow, T.J., Prystowsky, M.B., Childs, G., and Segall, J.E. (2015). MicroRNA-375 suppresses extracellular matrix degradation and Invadopodial activity in head and neck squamous cell carcinoma. Arch. Pathol. Lab. Med. 139, 1349–1361.10.1158/1538-7445.AM2015-185Search in Google Scholar

Kehl, T., Backes, C., Kern, F., Fehlmann, T., Ludwig, N., Meese, E., Lenhof, H.P., and Keller, A. (2017). About miRNAs, miRNA seeds, target genes and target pathways. Oncotarget 8, 107167–107175.10.18632/oncotarget.22363Search in Google Scholar PubMed PubMed Central

Klokk, T.I., Kilander, A., Xi, Z., Waehre, H., Risberg, B., Danielsen, H.E., and Saatcioglu, F. (2007). Kallikrein 4 is a proliferative factor that is overexpressed in prostate cancer. Cancer Res. 67, 5221–5230.10.1158/0008-5472.CAN-06-4728Search in Google Scholar PubMed

Larne, O., Ostling, P., Haflidadottir, B.S., Hagman, Z., Aakula, A., Kohonen, P., Kallioniemi, O., Edsjo, A., Bjartell, A., Lilja, H., et al. (2015). miR-183 in prostate cancer cells positively regulates synthesis and serum levels of prostate-specific antigen. Eur. Urol. 68, 581–588.10.1016/j.eururo.2014.12.025Search in Google Scholar PubMed

Lewis, B.P., Burge, C.B., and Bartel, D.P. (2005). Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120, 15–20.10.1016/j.cell.2004.12.035Search in Google Scholar PubMed

Lichner, Z., Mejia-Guerrero, S., Ignacak, M., Krizova, A., Bao, T.T., Girgis, A.H., Youssef, Y.M., and Yousef, G.M. (2012). Pleiotropic action of renal cell carcinoma-dysregulated miRNAs on hypoxia-related signaling pathways. Am. J. Pathol. 180, 1675–1687.10.1016/j.ajpath.2011.12.030Search in Google Scholar PubMed

Lichner, Z., Fendler, A., Saleh, C., Nasser, A.N., Boles, D., Al-Haddad, S., Kupchak, P., Dharsee, M., Nuin, P.S., Evans, K.R., et al. (2013). MicroRNA signature helps distinguish early from late biochemical failure in prostate cancer. Clin. Chem. 59, 1595–1603.10.1373/clinchem.2013.205450Search in Google Scholar PubMed

Loeb, S. and Catalona, W.J. (2014). The Prostate Health Index: a new test for the detection of prostate cancer. Ther. Adv. Urol. 6, 74–77.10.1177/1756287213513488Search in Google Scholar PubMed PubMed Central

Lopez, J.S. and Banerji, U. (2017). Combine and conquer: challenges for targeted therapy combinations in early phase trials. Nat. Rev. Clin. Oncol. 14, 57–66.10.1038/nrclinonc.2016.96Search in Google Scholar PubMed PubMed Central

Parekh, D.J., Punnen, S., Sjoberg, D.D., Asroff, S.W., Bailen, J.L., Cochran, J.S., Concepcion, R., David, R.D., Deck, K.B., Dumbadze, I., et al. (2015). A multi-institutional prospective trial in the USA confirms that the 4K score accurately identifies men with high-grade prostate cancer. Eur. Urol. 68, 464–470.10.1016/j.eururo.2014.10.021Search in Google Scholar PubMed

Pasic, M.D., Olkhov, E., Bapat, B., and Yousef, G.M. (2012). Epigenetic regulation of kallikrein-related peptidases: there is a whole new world out there. Biol. Chem. 393, 319–330.10.1515/hsz-2011-0273Search in Google Scholar PubMed

Pasic, M.D., Sotiropoulou, G., and Yousef, G.M. (2015). The miRNA-kallikrein interactions: adding a new dimension. Cell Cycle 14, 691–692.10.1080/15384101.2015.1006541Search in Google Scholar PubMed PubMed Central

Peng, Y. and Croce, C.M. (2016). The role of MicroRNAs in human cancer. Signal Transduct. Target Ther. 1, 15004.10.1038/sigtrans.2015.4Search in Google Scholar PubMed PubMed Central

Peterson, S.M., Thompson, J.A., Ufkin, M.L., Sathyanarayana, P., Liaw, L., and Congdon, C.B. (2014). Common features of microRNA target prediction tools. Front Genet. 5, 23.10.3389/fgene.2014.00023Search in Google Scholar PubMed PubMed Central

Prassas, I., Eissa, A., Poda, G., and Diamandis, E.P. (2015). Unleashing the therapeutic potential of human kallikrein-related serine proteases. Nat. Rev. Drug Discov. 14, 183–202.10.1038/nrd4534Search in Google Scholar PubMed

Samaan, S., Lichner, Z., Ding, Q., Saleh, C., Samuel, J., Streutker, C., and Yousef, G.M. (2014). Kallikreins are involved in an miRNA network that contributes to prostate cancer progression. Biol. Chem. 395, 991–1001.10.1515/hsz-2013-0288Search in Google Scholar PubMed

Seiz, L., Dorn, J., Kotzsch, M., Walch, A., Grebenchtchikov, N.I., Gkazepis, A., Schmalfeldt, B., Kiechle, M., Bayani, J., Diamandis, E.P., et al. (2012). Stromal cell-associated expression of kallikrein-related peptidase 6 (KLK6) indicates poor prognosis of ovarian cancer patients. Biol. Chem. 393, 391–401.10.1515/hsz-2011-0264Search in Google Scholar PubMed

Sells, E., Pandey, R., Chen, H., Skovan, B.A., Cui, H., and Ignatenko, N.A. (2017). Specific microRNA-mRNA regulatory network of colon cancer invasion mediated by tissue kallikrein-related peptidase 6. Neoplasia 19, 396–411.10.1016/j.neo.2017.02.003Search in Google Scholar PubMed PubMed Central

Shahinian, H., Loessner, D., Biniossek, M.L., Kizhakkedathu, J.N., Clements, J.A., Magdolen, V., and Schilling, O. (2014). Secretome and degradome profiling shows that Kallikrein-related peptidases 4, 5, 6, and 7 induce TGFbeta-1 signaling in ovarian cancer cells. Mol. Oncol. 8, 68–82.10.1016/j.molonc.2013.09.003Search in Google Scholar PubMed PubMed Central

Sidiropoulos, K.G., White, N.M., Bui, A., Ding, Q., Boulos, P., Pampalakis, G., Khella, H., Samuel, J.N., Sotiropoulou, G., and Yousef, G.M. (2014). Kallikrein-related peptidase 5 induces miRNA-mediated anti-oncogenic pathways in breast cancer. Oncoscience 1, 709–724.10.18632/oncoscience.91Search in Google Scholar PubMed PubMed Central

Sidiropoulos, K.G., Ding, Q., Pampalakis, G., White, N.M., Boulos, P., Sotiropoulou, G., and Yousef, G.M. (2016). KLK6-regulated miRNA networks activate oncogenic pathways in breast cancer subtypes. Mol. Oncol. 10, 993–1007.10.1016/j.molonc.2016.03.008Search in Google Scholar PubMed PubMed Central

Sotiropoulou, G., Pampalakis, G., and Diamandis, E.P. (2009). Functional roles of human kallikrein-related peptidases. J. Biol. Chem. 284, 32989–32994.10.1074/jbc.R109.027946Search in Google Scholar PubMed PubMed Central

Stefanini, A.C., da Cunha, B.R., Henrique, T., and Tajara, E.H. (2015). Involvement of kallikrein-related peptidases in normal and pathologic processes. Dis. Markers 2015, 946572.10.1155/2015/946572Search in Google Scholar PubMed PubMed Central

Stegeman, S., Amankwah, E., Klein, K., O’Mara, T.A., Kim, D., Lin, H.Y., Permuth-Wey, J., Sellers, T.A., Srinivasan, S., Eeles, R., et al. (2015). A large-scale analysis of genetic variants within putative miRNA binding sites in prostate cancer. Cancer Discov. 5, 368–379.10.1158/2159-8290.CD-14-1057Search in Google Scholar PubMed PubMed Central

Talieri, M., Devetzi, M., Scorilas, A., Pappa, E., Tsapralis, N., Missitzis, I., and Ardavanis, A. (2012). Human kallikrein-related peptidase 12 (KLK12) splice variants expression in breast cancer and their clinical impact. Tumour Biol. 33, 1075–1084.10.1007/s13277-012-0347-xSearch in Google Scholar PubMed

Tokas, T., Avgeris, M., Alamanis, C., Scorilas, A., Stravodimos, K.G., and Constantinides, C.A. (2017). Downregulated KLK13 expression in bladder cancer highlights tumor aggressiveness and unfavorable patients’ prognosis. J. Cancer Res. Clin. Oncol. 143, 521–532.10.1007/s00432-016-2301-6Search in Google Scholar PubMed

Tuccoli, A., Vitiello, M., Marranci, A., Russo, F., and Poliseno, L. (2016). Methods for the identification of PTEN-targeting microRNAs. Methods Mol. Biol. 1388, 111–138.10.1007/978-1-4939-3299-3_9Search in Google Scholar PubMed

Wang, S.M., Mao, J., Li, B., Wu, W., and Tang, L.L. (2008). Expression of KLK6 protein and mRNA in primary breast cancer and its clinical significance. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 24, 1087–1089.Search in Google Scholar

Wang, Z., Ruan, B., Jin, Y., Zhang, Y., Li, J., Zhu, L., Xu, W., Feng, L., Jin, H., and Wang, X. (2016). Identification of KLK10 as a therapeutic target to reverse trastuzumab resistance in breast cancer. Oncotarget 7, 79494–79502.10.18632/oncotarget.13104Search in Google Scholar PubMed PubMed Central

White, N.M., Bui, A., Mejia-Guerrero, S., Chao, J., Soosaipillai, A., Youssef, Y., Mankaruos, M., Honey, R.J., Stewart, R., Pace, K.T., et al. (2010a). Dysregulation of kallikrein-related peptidases in renal cell carcinoma: potential targets of miRNAs. Biol. Chem. 391, 411–423.10.1515/bc.2010.041Search in Google Scholar PubMed

White, N.M., Chow, T.F., Mejia-Guerrero, S., Diamandis, M., Rofael, Y., Faragalla, H., Mankaruous, M., Gabril, M., Girgis, A., and Yousef, G.M. (2010b). Three dysregulated miRNAs control kallikrein 10 expression and cell proliferation in ovarian cancer. Br. J. Cancer 102, 1244–1253.10.1038/sj.bjc.6605634Search in Google Scholar PubMed PubMed Central

White, N.M., Fatoohi, E., Metias, M., Jung, K., Stephan, C., and Yousef, G.M. (2011). Metastamirs: a stepping stone towards improved cancer management. Nat. Rev. Clin. Oncol. 8, 75–84.10.1038/nrclinonc.2010.173Search in Google Scholar PubMed

White, N.M., Youssef, Y.M., Fendler, A., Stephan, C., Jung, K., and Yousef, G.M. (2012). The miRNA-kallikrein axis of interaction: a new dimension in the pathogenesis of prostate cancer. Biol. Chem. 393, 379–389.10.1515/hsz-2011-0246Search in Google Scholar PubMed

Witkos, T.M., Koscianska, E., and Krzyzosiak, W.J. (2011). Practical aspects of microRNA target prediction. Curr. Mol. Med. 11, 93–109.10.2174/156652411794859250Search in Google Scholar PubMed PubMed Central

Xi, Z., Klokk, T.I., Korkmaz, K., Kurys, P., Elbi, C., Risberg, B., Danielsen, H., Loda, M., and Saatcioglu, F. (2004). Kallikrein 4 is a predominantly nuclear protein and is overexpressed in prostate cancer. Cancer Res. 64, 2365–2370.10.1158/0008-5472.CAN-03-2025Search in Google Scholar PubMed

Xi, S., Inchauste, S., Guo, H., Shan, J., Xiao, Z., Xu, H., Miettenen, M., Zhang, M.R., Hong, J.A., Raiji, M.T., et al. (2015). Cigarette smoke mediates epigenetic repression of miR-217 during esophageal adenocarcinogenesis. Oncogene 34, 5548–5559.10.1038/onc.2015.10Search in Google Scholar PubMed PubMed Central

Yang, F., Aubele, M., Walch, A., Gross, E., Napieralski, R., Zhao, S., Ahmed, N., Kiechle, M., Reuning, U., Dorn, J., et al. (2017). Tissue kallikrein-related peptidase 4 (KLK4), a novel biomarker in triple-negative breast cancer. Biol. Chem. 398, 1151–1164.10.1515/hsz-2017-0122Search in Google Scholar PubMed

Yoon, H., Blaber, S.I., Debela, M., Goettig, P., Scarisbrick, I.A., and Blaber, M. (2009). A completed KLK activome profile: investigation of activation profiles of KLK9, 10, and 15. Biol. Chem. 390, 373–377.10.1515/BC.2009.026Search in Google Scholar

Yousef, G.M. (2008). microRNAs: a new frontier in kallikrein research. Biol. Chem. 389, 689–694.10.1515/BC.2008.068Search in Google Scholar

Yousef, G.M., Kyriakopoulou, L.G., Scorilas, A., Fracchioli, S., Ghiringhello, B., Zarghooni, M., Chang, A., Diamandis, M., Giardina, G., Hartwick, W.J., et al. (2001). Quantitative expression of the human kallikrein gene 9 (KLK9) in ovarian cancer: a new independent and favorable prognostic marker. Cancer Res. 61, 7811–7818.Search in Google Scholar

Yousef, G.M., Yacoub, G.M., Polymeris, M.E., Popalis, C., Soosaipillai, A., and Diamandis, E.P. (2004). Kallikrein gene downregulation in breast cancer. Br. J. Cancer 90, 167–172.10.1038/sj.bjc.6601451Search in Google Scholar

Yousef, G.M., Obiezu, C.V., Luo, L.Y., Magklara, A., Borgono, C.A., Kishi, T., Memari, N., Michael, I.P., Sidiropoulos, M., Kurlender, L., et al. (2005). Human tissue kallikreins: from gene structure to function and clinical applications. Adv. Clin. Chem. 39, 11–79.10.1016/S0065-2423(04)39002-5Search in Google Scholar

Yu, Y., Prassas, I., and Diamandis, E.P. (2014). Putative kallikrein substrates and their (patho)biological functions. Biol. Chem. 395, 931–943.10.1515/hsz-2014-0129Search in Google Scholar PubMed

Zethelius, B., Berglund, L., Sundstrom, J., Ingelsson, E., Basu, S., Larsson, A., Venge, P., and Arnlov, J. (2008). Use of multiple biomarkers to improve the prediction of death from cardiovascular causes. N. Engl. J. Med. 358, 2107–2116.10.1056/NEJMoa0707064Search in Google Scholar PubMed

Received: 2017-12-20
Accepted: 2018-03-26
Published Online: 2018-03-31
Published in Print: 2018-09-25

©2018 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Highlight: The 7th International Symposium on Kallikreins and Kallikrein-Related Peptidases
  3. Obituary
  4. Manfred Schmitt (1947–2018)
  5. Functional interrelationships between the kallikrein-related peptidases family and the classical kinin system in the human neutrophil
  6. Overview of tissue kallikrein and kallikrein-related peptidases in breast cancer
  7. Kallikrein-related peptidases in lung diseases
  8. The miRNA-kallikrein interaction: a mosaic of epigenetic regulation in cancer
  9. Mining human cancer datasets for kallikrein expression in cancer: the ‘KLK-CANMAP’ Shiny web tool
  10. Specificity profiling of human trypsin-isoenzymes
  11. Activation and activity of glycosylated KLKs 3, 4 and 11
  12. Microenvironment proteinases, proteinase-activated receptor regulation, cancer and inflammation
  13. Kallikrein-related peptidase 6 orchestrates astrocyte form and function through proteinase activated receptor-dependent mechanisms
  14. Kallikrein-related peptidase 5 and seasonal influenza viruses, limitations of the experimental models for activating proteases
  15. Novel splice variants of the human kallikrein-related peptidases 11 (KLK11) and 12 (KLK12), unraveled by next-generation sequencing technology
  16. Insights into the activity control of the kallikrein-related peptidase 6: small-molecule modulators and allosterism
  17. Kallikrein-related peptidase 14 is the second KLK protease targeted by the serpin vaspin
  18. Profiling system for skin kallikrein proteolysis applied in gene-deficient mouse models
  19. Evidence that cell surface localization of serine protease activity facilitates cleavage of the protease activated receptor CDCP1
  20. Kallikrein-related peptidase 7 overexpression in melanoma cells modulates cell adhesion leading to a malignant phenotype
  21. KLK5, a novel potential suppressor of vaginal carcinogenesis
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