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Growth and survival of lung cancer cells: regulation by kallikrein-related peptidase 6 via activation of proteinase-activated receptor 2 and the epidermal growth factor receptor

  • Noémie Michel , Nathalie Heuzé-Vourc’h , Elise Lavergne , Christelle Parent , Marie-Lise Jourdan , Amandine Vallet , Sophie Iochmann , Orlando Musso , Pascale Reverdiau and Yves Courty EMAIL logo
Published/Copyright: March 19, 2014
Biological Chemistry
From the journal Biological Chemistry Volume 395 Issue 9

Abstract

The dysregulated expression of kallikrein-related peptidase 6 (KLK6) is involved in non-small cancer (NSCLC) cell growth. However, the mechanism that sustains KLK6 signaling remains unknown. We used an isogenic non-small cell lung cancer (NSCLC) cell model system to demonstrate that KLK6 promotes the proliferation of lung tumoral cells and restrains their apoptosis in vitro via ligand-dependent EGFR transactivation. KLK6 activated the ERK and Akt pathways and triggered the nuclear translocation of β-catenin. The stimulating effects of KLK6 required its proteolytic activity and were dependent on the protease-activated receptor 2 (PAR2). These observations support the concept of a role for KLK6 in the oncogenesis of NSCLC.

Keywords: EGFR; kallikrein-related peptidases; lung cancer; PAR
Corresponding author: Yves Courty, INSERM UMR1100, Centre d’Etude des Pathologies Respiratoires, 10 boulevard Tonnellé, F-37032 Tours cedex, France, e-mail:
aNoémie Michel and Nathalie Heuzé-Vourc’h contributed equally to the work.

Acknowledgments

The English text was edited by Dr. Owen Parkes. Financial support was provided by the Ligue Contre le Cancer (Comités d’Indre et d’Eure et Loire) and Région Centre (grant KalliCap). Noémie Michel was the recipient of a Fellowship from the Région Centre.

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Received: 2014-2-12
Accepted: 2014-3-13
Published Online: 2014-3-19
Published in Print: 2014-9-1

©2014 by De Gruyter

Articles in the same Issue

  1. Frontmatter
  2. Guest Editorial
  3. Highlight: The 5th International Symposium on Kallikreins and Kallikrein-Related Peptidases
  4. KLKs and their hormone-like signaling actions: a new life for the PSA-KLK family
  5. Putative kallikrein substrates and their (patho)biological functions
  6. Netherton syndrome: defective kallikrein inhibition in the skin leads to skin inflammation and allergy
  7. Sweetened kallikrein-related peptidases (KLKs): glycan trees as potential regulators of activation and activity
  8. Activation of membrane-bound proteins and receptor systems: a link between tissue kallikrein and the KLK-related peptidases
  9. Kallikreins are involved in an miRNA network that contributes to prostate cancer progression
  10. Evolution of Klk4 and enamel maturation in eutherians
  11. Growth and survival of lung cancer cells: regulation by kallikrein-related peptidase 6 via activation of proteinase-activated receptor 2 and the epidermal growth factor receptor
  12. CrataBL, a lectin and Factor Xa inhibitor, plays a role in blood coagulation and impairs thrombus formation
  13. Mining for single nucleotide variants (SNVs) at the kallikrein locus with predicted functional consequences
  14. Low mRNA expression levels of kallikrein-related peptidase 4 (KLK4) predict short-term relapse in patients with laryngeal squamous cell carcinoma
  15. Differential expression of multiple kallikreins in a viral model of multiple sclerosis points to unique roles in the innate and adaptive immune response
  16. Kallikrein-related peptidase 7 (KLK7) is a proliferative factor that is aberrantly expressed in human colon cancer
  17. Prognostic significance of human tissue kallikrein-related peptidases 6 and 10 in gastric cancer
  18. 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
  19. Kallikrein-related peptidase 6 (KLK6) expression in the progression of colon adenoma to carcinoma
  20. Development of monoclonal antibodies to human kallikrein-related peptidase 6 (KLK6) and their use in an immunofluorometric assay for free KLK6
  21. Analysis of androgen and anti-androgen regulation of KLK-related peptidase 2, 3, and 4 alternative transcripts in prostate cancer
https://doi.org/10.1515/hsz-2014-0124
Keywords for this article
EGFR; kallikrein-related peptidases; lung cancer; PAR

Articles in the same Issue

  1. Frontmatter
  2. Guest Editorial
  3. Highlight: The 5th International Symposium on Kallikreins and Kallikrein-Related Peptidases
  4. KLKs and their hormone-like signaling actions: a new life for the PSA-KLK family
  5. Putative kallikrein substrates and their (patho)biological functions
  6. Netherton syndrome: defective kallikrein inhibition in the skin leads to skin inflammation and allergy
  7. Sweetened kallikrein-related peptidases (KLKs): glycan trees as potential regulators of activation and activity
  8. Activation of membrane-bound proteins and receptor systems: a link between tissue kallikrein and the KLK-related peptidases
  9. Kallikreins are involved in an miRNA network that contributes to prostate cancer progression
  10. Evolution of Klk4 and enamel maturation in eutherians
  11. Growth and survival of lung cancer cells: regulation by kallikrein-related peptidase 6 via activation of proteinase-activated receptor 2 and the epidermal growth factor receptor
  12. CrataBL, a lectin and Factor Xa inhibitor, plays a role in blood coagulation and impairs thrombus formation
  13. Mining for single nucleotide variants (SNVs) at the kallikrein locus with predicted functional consequences
  14. Low mRNA expression levels of kallikrein-related peptidase 4 (KLK4) predict short-term relapse in patients with laryngeal squamous cell carcinoma
  15. Differential expression of multiple kallikreins in a viral model of multiple sclerosis points to unique roles in the innate and adaptive immune response
  16. Kallikrein-related peptidase 7 (KLK7) is a proliferative factor that is aberrantly expressed in human colon cancer
  17. Prognostic significance of human tissue kallikrein-related peptidases 6 and 10 in gastric cancer
  18. 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
  19. Kallikrein-related peptidase 6 (KLK6) expression in the progression of colon adenoma to carcinoma
  20. Development of monoclonal antibodies to human kallikrein-related peptidase 6 (KLK6) and their use in an immunofluorometric assay for free KLK6
  21. Analysis of androgen and anti-androgen regulation of KLK-related peptidase 2, 3, and 4 alternative transcripts in prostate cancer
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