Proteolytic Processing of Laminin-332 by Hepsin and Matriptase and Its Role in Prostate Cancer Progression PRINCIPAL INVESTIGATOR:
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TMEFF2 shedding is regulated by oxidative stress and mediated by ADAMs and transmembrane serine proteases implicated in prostate cancer
TMEFF2 is a type I transmembrane protein with two follistatin (FS) and one EGF-like domain over-expressed in prostate cancer; however its biological role in prostate cancer development and progression remains unclear, which may, at least in part, be explained by its proteolytic processing. The extracellular part of TMEFF2 (TMEFF2-ECD) is cleaved by ADAM17 and the membrane-retained fragment is f...
متن کاملPotent and specific inhibition of the biological activity of the type-II transmembrane serine protease matriptase by the cyclic microprotein MCoTI-II.
Matriptase is a type-II transmembrane serine protease involved in epithelial homeostasis in both health and disease, and is implicated in the development and progression of a variety of cancers. Matriptase mediates its biological effects both via as yet undefined substrates and pathways, and also by proteolytic cleavage of a variety of well-defined protein substrates, several of which it shares...
متن کاملPericellular activation of hepatocyte growth factor by the transmembrane serine proteases matriptase and hepsin, but not by the membrane-associated protease uPA.
HGF (hepatocyte growth factor) is a pleiotropic cytokine homologous to the serine protease zymogen plasminogen that requires canonical proteolytic cleavage to gain functional activity. The activating proteases are key components of its regulation, but controversy surrounds their identity. Using quantitative analysis we found no evidence for activation by uPA (urokinase plasminogen activator), d...
متن کاملPro-urokinase-type plasminogen activator is a substrate for hepsin.
Hepsin, a type II transmembrane serine protease, is strongly up-regulated in prostate cancer. Hepsin overexpression in a mouse prostate cancer model resulted in tumor progression and metastasis, associated with basement membrane disorganization. We investigated whether hepsin enzymatic activity was linked to the basement membrane defects by examining its ability to initiate the plasminogen/plas...
متن کاملTumor and Stem Cell Biology Androgen-Induced TMPRSS2 Activates Matriptase and Promotes Extracellular Matrix Degradation, Prostate Cancer Cell Invasion, Tumor Growth, and Metastasis
Dysregulation of androgen signaling and pericellular proteolysis is necessary for prostate cancer progression, but the links between them are still obscure. In this study, we show how the membrane-anchored serine protease TMPRSS2 stimulates a proteolytic cascade that mediates androgen-induced prostate cancer cell invasion, tumor growth, and metastasis. We found that matriptase serves as a subst...
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تاریخ انتشار 2010