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

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...

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Autores principales: Yamasaki, Koji, Mukai, Shoichiro, Nagai, Takahiro, Nakahara, Kozue, Fujii, Masato, Terada, Naoki, Ohno, Akinobu, Sato, Yuichiro, Toda, Yoshinobu, Kataoka, Hiroaki, Kamoto, Toshiyuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321379/
https://www.ncbi.nlm.nih.gov/pubmed/30469509
http://dx.doi.org/10.3390/ijms19123708
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author Yamasaki, Koji
Mukai, Shoichiro
Nagai, Takahiro
Nakahara, Kozue
Fujii, Masato
Terada, Naoki
Ohno, Akinobu
Sato, Yuichiro
Toda, Yoshinobu
Kataoka, Hiroaki
Kamoto, Toshiyuki
author_facet Yamasaki, Koji
Mukai, Shoichiro
Nagai, Takahiro
Nakahara, Kozue
Fujii, Masato
Terada, Naoki
Ohno, Akinobu
Sato, Yuichiro
Toda, Yoshinobu
Kataoka, Hiroaki
Kamoto, Toshiyuki
author_sort Yamasaki, Koji
collection PubMed
description 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.
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spelling pubmed-63213792019-01-07 Matriptase-Induced Phosphorylation of MET is Significantly Associated with Poor Prognosis in Invasive Bladder Cancer; an Immunohistochemical Analysis Yamasaki, Koji Mukai, Shoichiro Nagai, Takahiro Nakahara, Kozue Fujii, Masato Terada, Naoki Ohno, Akinobu Sato, Yuichiro Toda, Yoshinobu Kataoka, Hiroaki Kamoto, Toshiyuki Int J Mol Sci Article 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. MDPI 2018-11-22 /pmc/articles/PMC6321379/ /pubmed/30469509 http://dx.doi.org/10.3390/ijms19123708 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yamasaki, Koji
Mukai, Shoichiro
Nagai, Takahiro
Nakahara, Kozue
Fujii, Masato
Terada, Naoki
Ohno, Akinobu
Sato, Yuichiro
Toda, Yoshinobu
Kataoka, Hiroaki
Kamoto, Toshiyuki
Matriptase-Induced Phosphorylation of MET is Significantly Associated with Poor Prognosis in Invasive Bladder Cancer; an Immunohistochemical Analysis
title Matriptase-Induced Phosphorylation of MET is Significantly Associated with Poor Prognosis in Invasive Bladder Cancer; an Immunohistochemical Analysis
title_full Matriptase-Induced Phosphorylation of MET is Significantly Associated with Poor Prognosis in Invasive Bladder Cancer; an Immunohistochemical Analysis
title_fullStr Matriptase-Induced Phosphorylation of MET is Significantly Associated with Poor Prognosis in Invasive Bladder Cancer; an Immunohistochemical Analysis
title_full_unstemmed Matriptase-Induced Phosphorylation of MET is Significantly Associated with Poor Prognosis in Invasive Bladder Cancer; an Immunohistochemical Analysis
title_short Matriptase-Induced Phosphorylation of MET is Significantly Associated with Poor Prognosis in Invasive Bladder Cancer; an Immunohistochemical Analysis
title_sort matriptase-induced phosphorylation of met is significantly associated with poor prognosis in invasive bladder cancer; an immunohistochemical analysis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321379/
https://www.ncbi.nlm.nih.gov/pubmed/30469509
http://dx.doi.org/10.3390/ijms19123708
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