FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2968697750> ?p ?o ?g. }

• W2968697750 abstract "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 associated with low expression levels of wild-type hepsin, but were partially lost in response to overexpression. Instead, overexpression of wild-type hepsin, but not of HPN S353A , induced relocalization of the protein to the cytoplasm, and increased autophagic flux in vitro as well as LC3B punctae frequency in tumor xenografts. Confocal microscopy revealed colocalization of wild-type hepsin with both LC3B punctae as well as with the autophagy cargo receptor p62/SQSTM1. Overexpression of wild type, but not protease-deficient hepsin induced expression and nuclear presence of CHOP, indicating activation of the unfolded protein response and ER-associated protein degradation (ERAD). Whereas inhibitors of ER stress and secretory protein trafficking slightly increased viability, combined inhibition of the ubiquitin-proteasome degradation pathway (by bortezomib) with either ER stress (by salubrinal) or autophagy (by bafilomycin A1) revealed a significant decrease of viability during overexpression of wild-type hepsin in PC-3 cells. Our results demonstrate that a precise control of Hepsin proteolytic activity is critical for PCa cell fate and suggest, that the interference with ERAD could be a promising therapeutic option, leading to induction of proteotoxicity in hepsin-overexpressing tumors." @default.
• W2968697750 created "2019-08-22" @default.
• W2968697750 creator A5018364981 @default.
• W2968697750 creator A5034829718 @default.
• W2968697750 creator A5048124219 @default.
• W2968697750 creator A5056973287 @default.
• W2968697750 creator A5060121870 @default.
• W2968697750 creator A5061644837 @default.
• W2968697750 date "2019-08-09" @default.
• W2968697750 modified "2023-10-10" @default.
• W2968697750 title "Excess hepsin proteolytic activity limits oncogenic signaling and induces ER stress and autophagy in prostate cancer cells" @default.
• W2968697750 cites W1528543854 @default.
• W2968697750 cites W1546741081 @default.
• W2968697750 cites W1956057741 @default.
• W2968697750 cites W1969275365 @default.
• W2968697750 cites W1976697710 @default.
• W2968697750 cites W1980792579 @default.
• W2968697750 cites W1990054050 @default.
• W2968697750 cites W1999836692 @default.
• W2968697750 cites W2006130746 @default.
• W2968697750 cites W2012080977 @default.
• W2968697750 cites W2012411473 @default.
• W2968697750 cites W2012627890 @default.
• W2968697750 cites W2018307268 @default.
• W2968697750 cites W2019192392 @default.
• W2968697750 cites W2025665129 @default.
• W2968697750 cites W2031735388 @default.
• W2968697750 cites W2036902495 @default.
• W2968697750 cites W2037562795 @default.
• W2968697750 cites W2052641699 @default.
• W2968697750 cites W2060396407 @default.
• W2968697750 cites W2067602854 @default.
• W2968697750 cites W2067782874 @default.
• W2968697750 cites W2072308516 @default.
• W2968697750 cites W2072948437 @default.
• W2968697750 cites W2080878773 @default.
• W2968697750 cites W2085788734 @default.
• W2968697750 cites W2118488518 @default.
• W2968697750 cites W2122976061 @default.
• W2968697750 cites W2129574945 @default.
• W2968697750 cites W2131994406 @default.
• W2968697750 cites W2140487984 @default.
• W2968697750 cites W2140552191 @default.
• W2968697750 cites W2146754019 @default.
• W2968697750 cites W2160864910 @default.
• W2968697750 cites W2168453644 @default.
• W2968697750 cites W2170828959 @default.
• W2968697750 cites W2172085426 @default.
• W2968697750 cites W2214858649 @default.
• W2968697750 cites W2420981549 @default.
• W2968697750 cites W2561943186 @default.
• W2968697750 cites W2593836869 @default.
• W2968697750 cites W2803862531 @default.
• W2968697750 cites W2890999095 @default.
• W2968697750 cites W2893889295 @default.
• W2968697750 cites W93762695 @default.
• W2968697750 doi "https://doi.org/10.1038/s41419-019-1830-8" @default.
• W2968697750 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7016119" @default.
• W2968697750 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32051394" @default.
• W2968697750 hasPublicationYear "2019" @default.
• W2968697750 type Work @default.
• W2968697750 sameAs 2968697750 @default.
• W2968697750 citedByCount "17" @default.
• W2968697750 countsByYear W29686977502020 @default.
• W2968697750 countsByYear W29686977502021 @default.
• W2968697750 countsByYear W29686977502022 @default.
• W2968697750 countsByYear W29686977502023 @default.
• W2968697750 crossrefType "journal-article" @default.
• W2968697750 hasAuthorship W2968697750A5018364981 @default.
• W2968697750 hasAuthorship W2968697750A5034829718 @default.
• W2968697750 hasAuthorship W2968697750A5048124219 @default.
• W2968697750 hasAuthorship W2968697750A5056973287 @default.
• W2968697750 hasAuthorship W2968697750A5060121870 @default.
• W2968697750 hasAuthorship W2968697750A5061644837 @default.
• W2968697750 hasBestOaLocation W29686977501 @default.
• W2968697750 hasConcept C139447449 @default.
• W2968697750 hasConcept C158617107 @default.
• W2968697750 hasConcept C185592680 @default.
• W2968697750 hasConcept C190283241 @default.
• W2968697750 hasConcept C203522944 @default.
• W2968697750 hasConcept C27740335 @default.
• W2968697750 hasConcept C502942594 @default.
• W2968697750 hasConcept C55493867 @default.
• W2968697750 hasConcept C86803240 @default.
• W2968697750 hasConcept C95444343 @default.
• W2968697750 hasConceptScore W2968697750C139447449 @default.
• W2968697750 hasConceptScore W2968697750C158617107 @default.
• W2968697750 hasConceptScore W2968697750C185592680 @default.
• W2968697750 hasConceptScore W2968697750C190283241 @default.
• W2968697750 hasConceptScore W2968697750C203522944 @default.
• W2968697750 hasConceptScore W2968697750C27740335 @default.
• W2968697750 hasConceptScore W2968697750C502942594 @default.
• W2968697750 hasConceptScore W2968697750C55493867 @default.
• W2968697750 hasConceptScore W2968697750C86803240 @default.
• W2968697750 hasConceptScore W2968697750C95444343 @default.
• W2968697750 hasFunder F4320320879 @default.
• W2968697750 hasIssue "8" @default.
• W2968697750 hasLocation W29686977501 @default.
• W2968697750 hasLocation W29686977502 @default.
• W2968697750 hasLocation W29686977503 @default.

• next