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 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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High Expression of Karyopherin-α2 Defines Poor Prognosis in Non–Muscle-Invasive Bladder Cancer and in Patients with Invasive Bladder Cancer Undergoing Radical Cystectomy

European Urology ◽

10.1016/j.eururo.2011.01.048 ◽

2011 ◽

Vol 59 (5) ◽

pp. 841-848 ◽

Cited By ~ 51

Author(s):

Jørgen Bjerggaard Jensen ◽

Pia Pinholt Munksgaard ◽

Christoffer Mørk Sørensen ◽

Niels Fristrup ◽

Karin Birkenkamp-Demtroder ◽

...

Keyword(s):

Bladder Cancer ◽

Radical Cystectomy ◽

Poor Prognosis ◽

High Expression ◽

Invasive Bladder Cancer ◽

Muscle Invasive Bladder Cancer ◽

Muscle Invasive

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Enhanced Expression of CNTD2/CCNP Predicts Poor Prognosis in Bladder Cancer Based on the GSE13507

Frontiers in Genetics ◽

10.3389/fgene.2021.579900 ◽

2021 ◽

Vol 12 ◽

Author(s):

Mancheng Gong ◽

Erlin Song ◽

Guiying Huang ◽

Wenjun Ni ◽

Wenjing Dong ◽

...

Keyword(s):

Bladder Cancer ◽

Cancer Patients ◽

Cancer Progression ◽

Poor Prognosis ◽

Malignant Tumors ◽

High Expression ◽

Prognostic Indicators ◽

Bladder Tissue ◽

Normal Bladder ◽

Tcga Dataset

Bladder cancer is one of the most common urogenital malignancies in the world, and there are no adequate prognostic indicators. CNTD2 is one of the atypical cyclins, which may be related to the cell cycle and even the development of cancers. Early studies have shown that CNTD2 is closely related to the occurrence and development of many malignant tumors. However, the mechanism of CNTD2 in bladder cancer has not been reported. In our research, we explored the different expressions of CNTD2 between 411 bladder cancers and 19 normal bladder tissues based on the TCGA dataset. CNTD2-related signaling pathways were identified through the GSEA. We analyzed the associations of CNTD2 expression and bladder cancer progression and survival using GSE13507. Compared with 19 cases of normal bladder tissue, CNTD2 gene expression was increased in 411 cases of bladder cancer. The high expression of CNTD2 strongly correlated with grade (P < 0.0001), T classification (P = 0.0001), N classification (P = 0.00011), M classification (P = 0.044), age (P = 0.027), and gender (P = 0.0012). Bladder cancer patients with high CNTD2 expression had shorter overall survival (P < 0.001). In the meantime, univariate and multivariate analyses showed that the increased expression of CNTD2 was an independent factor for poor prognosis in bladder cancer patients (P < 0.001 and P < 0.001, respectively). CNTD2 expression is closely related to bladder cancer progression, and the high expression of CNTD2 may be an adverse biomarker in bladder cancer patients.

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A genetic variant conferred high expression of CAV2 promotes pancreatic cancer progression and associates with poor prognosis

European Journal of Cancer ◽

10.1016/j.ejca.2021.04.008 ◽

2021 ◽

Vol 151 ◽

pp. 94-105

Author(s):

Ying Zhu ◽

Jianbo Tian ◽

Xiating Peng ◽

Xiaoyang Wang ◽

Nan Yang ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Progression ◽

Poor Prognosis ◽

Genetic Variant ◽

High Expression

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Type II transmembrane serine proteases as potential targets for cancer therapy

Biological Chemistry ◽

10.1515/hsz-2016-0131 ◽

2016 ◽

Vol 397 (9) ◽

pp. 815-826 ◽

Cited By ~ 23

Author(s):

Andrew S. Murray ◽

Fausto A. Varela ◽

Karin List

Keyword(s):

Cancer Progression ◽

Serine Proteases ◽

Molecular Mechanisms ◽

Inflammatory Cells ◽

Activity Levels ◽

Type Ii ◽

Neoplastic Progression ◽

Treatment Regimens ◽

Proinflammatory Mediators ◽

Transmembrane Serine Protease

Abstract Carcinogenesis is accompanied by increased protein and activity levels of extracellular cell-surface proteases that are capable of modifying the tumor microenvironment by directly cleaving the extracellular matrix, as well as activating growth factors and proinflammatory mediators involved in proliferation and invasion of cancer cells, and recruitment of inflammatory cells. These complex processes ultimately potentiate neoplastic progression leading to local tumor cell invasion, entry into the vasculature, and metastasis to distal sites. Several members of the type II transmembrane serine protease (TTSP) family have been shown to play critical roles in cancer progression. In this review the knowledge collected over the past two decades about the molecular mechanisms underlying the pro-cancerous properties of selected TTSPs will be summarized. Furthermore, we will discuss how these insights may facilitate the translation into clinical settings in the future by specifically targeting TTSPs as part of novel cancer treatment regimens.

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