title: 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.
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.
authors.forename: Noémie
authors.initials: N
authors.lastname: Michel
authors.forename: Nathalie
authors.initials: N
authors.lastname: Heuzé-Vourc'h
authors.forename: Elise
authors.initials: E
authors.lastname: Lavergne
authors.forename: Christelle
authors.initials: C
authors.lastname: Parent
authors.forename: Marie-Lise
authors.initials: ML
authors.lastname: Jourdan
authors.forename: Amandine
authors.initials: A
authors.lastname: Vallet
authors.forename: Sophie
authors.initials: S
authors.lastname: Iochmann
authors.forename: Orlando
authors.initials: O
authors.lastname: Musso
authors.forename: Pascale
authors.initials: P
authors.lastname: Reverdiau
authors.forename: Yves
authors.initials: Y
authors.lastname: Courty
mesh_terms: D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival; D066246:ErbB Receptors / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D020868:Gene Silencing; D006801:Humans; D007610:Kallikreins / Q000378:metabolism*; D008024:Ligands; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D050505:Mutant Proteins / Q000378:metabolism; D010766:Phosphorylation; D021381:Protein Transport; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D044464:Receptor, PAR-2 / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D015820:Cadherins; D008024:Ligands; D050505:Mutant Proteins; D044464:Receptor, PAR-2; D051176:beta Catenin; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; C103551:KLK6 protein, human; D007610:Kallikreins