Polyserase-1/TMPRSS9 induces pro-tumor effects in pancreatic cancer cells by activation of pro-uPA

Abstract

Abstract. Polyserase-1/TMPRSS9 is a type II transmembrane serine protease showing a complex molecular architecture characterized by the presence of three tandem serine protease domains in its amino acid sequence. This protease is widely expressed in mouse and human tissues, however, its functional significance is unknown in both normal and pathological conditions. In the present study, we evaluated the possible role of polyserase-1 in cancer progression. First, we showed that polyserase-1 increased the invasive capacities of PANC-1 and SK-PC-3 pancreatic cancer cells. Moreover, the presence of polyserase-1 enhanced anchorage-independent growth and diminished the adhesion capability of PANC-1 cells to different extracellular matrix components. These effects were mediated by the efficient conversion of pro-uPA to active uPA and high phosphorylation levels of ERK detected in the PANC-1 cells expressing exogenous polyserase-1. Collectively, our data suggest that polyserase-1 may be involved in cancer progression and, similarly to what has been proposed for the closely related serine proteases matriptase and TMPRSS4, inhibition of TMPRSS9 activity may contribute to the inhibition of tumor growth.

Functional Genomic Analysis of the Impact of Camelina (Camelina sativa) Meal on Atlantic Salmon (Salmo salar) Distal Intestine Gene Expression and Physiology

“…Tmprss9 , also commonly known as polyserase-I , was first characterized in Cal et al ( 2003 ). It has been identified as a pro-tumor protease in epithelioid carcinomas (cell line PANC-1) and adenocarcinomas (cell line SK-PC-1) of the pancreas (Fontanil et al 2014 ). Cancerous cells demonstrating tmprss9 expression were found to have significant activation of the urokinase plasminogen activator (uPA) system, which is heavily involved in remodeling of the extracellular matrix (ECM) for the promotion of tumor progression and metastasis (Okumura et al 2006 ; Ulisse et al 2009 ; Fontanil et al 2014 ).…”

Priming of SARS-CoV-2 S protein by several membrane-bound serine proteinases could explain enhanced viral infectivity and systemic COVID-19 infection

“…Further, TMPRSS3, TMPRSS4, matriptase and prostasin have all been reported as ENaC activators (38)(39)(40)(41)(42). Several MASPs cleave and activate pro-uPA (24,32,(43)(44)(45)(46), presumably bound to its cell surface receptor, uPAR, which is additionally targeted by TMPRSS11D (47). Both hepsin and matriptase have been identified as efficient, physiologically relevant activators of pro-HGF (43,(48)(49)(50) and of the matrix metalloproteinases, proMMP-1 and -3 (36,51,52).…”

Transcriptomic Response of Breast Cancer Cells MDA-MB-231 to Docosahexaenoic Acid: Downregulation of Lipid and Cholesterol Metabolism Genes and Upregulation of Genes of the Pro-Apoptotic ER-Stress Pathway

“…Two of the proteases are active and can be inhibited by serine protease inhibitors, and one is thought to be catalytically inactive. The TMPRSS9 expression was reported to enhance the invasive capability of pancreatic cancer cells [93] and may be involved in cancer progression. Therefore, the two-fold downregulation of TMPRSS9 may account, at least in part, for the reduction of the invasive phenotype of MDA-MB-231 cells.…”