title: The tyrosine kinase c-Met contributes to the pro-tumorigenic function of the p38 kinase in human bile duct cholangiocarcinoma cells.
abstract: Pro-tumorigenic function of the p38 kinase plays a critical role in human cholangiocarcinogenesis. However, the underlying mechanism remains incompletely understood. Here, we report that c-Met, the tyrosine kinase receptor for hepatocyte growth factor (HGF), contributes to the pro-tumorigenic ability of p38 in human cholangiocarcinoma cells. Both p38 and c-Met promote the proliferation and invasion of human cholangiocarcinoma cells. Importantly, inhibition or knockdown of p38 decreased the basal activation of c-Met. Tyrosine phosphatase inhibitor studies revealed that p38 promotes the activity of c-Met, at least in part, by inhibiting dephosphorylation of the receptor. Moreover, density enhanced phosphatase-1 (DEP-1) is involved in p38-mediated inhibiting dephosphorylation of c-Met. Furthermore, p38 inhibits the degradation of c-Met. Taken together, these data provide a potential mechanism to explain how p38 promotes human cholangiocarcinoma cell proliferation and invasion. We propose that the link between p38 and c-Met is implicated in the progression of human cholangiocarcinoma.
authors.affiliation: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438.
authors.forename: Rongyang
authors.initials: R
authors.lastname: Dai
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Fu
authors.forename: Yao
authors.initials: Y
authors.lastname: Chen
authors.forename: Ruoyu
authors.initials: R
authors.lastname: Wang
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Zhao
authors.forename: Tao
authors.initials: T
authors.lastname: Luo
authors.forename: Junjie
authors.initials: J
authors.lastname: Zhu
authors.forename: Yibin
authors.initials: Y
authors.lastname: Ren
authors.forename: Jie
authors.initials: J
authors.lastname: Cao
authors.forename: Youwen
authors.initials: Y
authors.lastname: Qian
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.forename: Hongyang
authors.initials: H
authors.lastname: Wang
mesh_terms: D001650:Bile Duct Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation; D018281:Cholangiocarcinoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D056945:Hep G2 Cells; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009361:Neoplasm Invasiveness; D010766:Phosphorylation / Q000235:genetics; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism*; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3 / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: C066855:HGF protein, human; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D048051:p38 Mitogen-Activated Protein Kinases; C486288:PTPRJ protein, human; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3