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Open AccessArticle

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

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Department of Urology, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan
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Section of Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan
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Section of Diagnostic Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan
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Department of Clinical Laboratory Science, Tenri Health Care University, Nara 632-0018, Japan
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Oncopathology and Regenerative Biology Section, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(12), 3708; https://doi.org/10.3390/ijms19123708
Received: 27 September 2018 / Revised: 13 November 2018 / Accepted: 20 November 2018 / Published: 22 November 2018
(This article belongs to the Special Issue Hepatocyte Growth Factor (HGF))
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. View Full-Text
Keywords: matriptase; hepatocyte growth factor; MET; bladder cancer matriptase; hepatocyte growth factor; MET; bladder cancer
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Yamasaki, K.; Mukai, S.; Nagai, T.; Nakahara, K.; Fujii, M.; Terada, N.; Ohno, A.; Sato, Y.; Toda, Y.; Kataoka, H.; Kamoto, T. Matriptase-Induced Phosphorylation of MET is Significantly Associated with Poor Prognosis in Invasive Bladder Cancer; an Immunohistochemical Analysis. Int. J. Mol. Sci. 2018, 19, 3708.

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