Matriptase-Induced Phosphorylation of MET is Significantly Associated with Poor Prognosis in Invasive Bladder Cancer; an Immunohistochemical Analysis

International Journal of Molecular Sciences

Yoshinobu Toda¹  Takahiro Nagai²  Shoichiro Mukai²  Naoki Terada²  Toshiyuki Kamoto²  Kozue Nakahara²  Masato Fujii²  Koji Yamasaki²  Hiroaki Kataoka³  Yuichiro Sato⁴  Akinobu Ohno⁵ 

[1] Department of Clinical Laboratory Science, Tenri Health Care University, Nara 632-0018, Japan;Department of Urology, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan;Oncopathology and Regenerative Biology Section, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan;Section of Diagnostic Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan;Section of Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan;

关键词: matriptase;    hepatocyte growth factor;    MET;    bladder cancer;   

DOI  :  10.3390/ijms19123708

来源: DOAJ

【 摘 要 】

Hepatocyte growth factor (HGF) plays an important role in cancer progression via phosphorylation of MET (c-met proto-oncogene product, receptor of HGF). HGF-zymogen (pro-HGF) must be processed for activation by HGF activators including matriptase, which is a type II transmembrane serine protease and the most efficient activator. The enzymatic activity is tightly regulated by HGF activator inhibitors (HAIs). Dysregulated pro-HGF activation (with upregulated MET phosphorylation) is reported to promote cancer progression in various cancers. We retrospectively analyzed the expression of matriptase, phosphorylated-MET (phospho-MET) and HAI-1 in tumor specimens obtained from patients with invasive bladder cancer by immunohistochemistry. High expression of phospho-MET and increased expression of matriptase were significantly associated with poor prognosis, and high matriptase/low HAI-1 expression showed poorer prognosis. Furthermore, high expression of matriptase tended to correlate with phosphorylation of MET. Increased expression of matriptase may induce the ligand-dependent activation of MET, which leads to poor prognosis in patients with invasive bladder cancer.

【 授权许可】

Unknown