title: Polyserase-1/TMPRSS9 induces pro-tumor effects in pancreatic cancer cells by activation of pro-uPA.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Oviedo, 33006 Oviedo, Asturias, Spain.
authors.forename: Tania
authors.initials: T
authors.lastname: Fontanil
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Oviedo, 33006 Oviedo, Asturias, Spain.
authors.forename: Yamina
authors.initials: Y
authors.lastname: Mohamedi
authors.affiliation: University Institute of Oncology of Principado de Asturias (UOPA), University of Oviedo, 33006 Oviedo, Asturias, Spain.
authors.forename: Manuel M
authors.initials: MM
authors.lastname: Esteban
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Oviedo, 33006 Oviedo, Asturias, Spain.
authors.forename: Alvaro J
authors.initials: AJ
authors.lastname: Obaya
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Oviedo, 33006 Oviedo, Asturias, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Cal
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D012697:Serine Endopeptidases / Q000096:biosynthesis* / Q000235:genetics; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D012697:Serine Endopeptidases; C477599:polyserase I, human; D014568:Urokinase-Type Plasminogen Activator