Excess hepsin proteolytic activity limits oncogenic signaling and induces ER stress and autophagy in prostate cancer cells.

ABSTRACT: The serine protease hepsin is frequently overexpressed in human prostate cancer (PCa) and is associated with matrix degradation and PCa progression in mice. Curiously, low expression of hepsin is associated with poor survival in different cancer types, and transgenic overexpression of hepsin leads to loss of viability in various cancer cell lines. Here, by comparing isogenic transfectants of the PCa cell line PC-3 providing inducible overexpression of wild-type hepsin (HPN) vs. the protease-deficient mutant HPN^S353A, we were able to attribute hepsin-mediated tumor-adverse effects to its excess proteolytic activity. A stem-like expression signature of surface markers and adhesion molecules, Notch intracellular domain release, and increased pericellular protease activity were asso

SUBMITTER: Willbold R 

PROVIDER: S-EPMC6689070 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature