Matches in SemOpenAlex for { <https://semopenalex.org/work/W3026177074> ?p ?o ?g. }
- W3026177074 endingPage "1340" @default.
- W3026177074 startingPage "1340" @default.
- W3026177074 abstract "The requirement of the E3 ubiquitin-ligase Hakai for the ubiquitination and subsequent degradation of E-cadherin has been associated with enhanced epithelial-to-mesenchymal transition (EMT), tumour progression and carcinoma metastasis. To date, most of the reported EMT-related inhibitors were not developed for anti-EMT purposes, but indirectly affect EMT. On the other hand, E3 ubiquitin-ligase enzymes have recently emerged as promising therapeutic targets, as their specific inhibition would prevent wider side effects. Given this background, a virtual screening was performed to identify novel specific inhibitors of Hakai, targeted against its phosphotyrosine-binding pocket, where phosphorylated-E-cadherin specifically binds. We selected a candidate inhibitor, Hakin-1, which showed an important effect on Hakai-induced ubiquitination. Hakin-1 also inhibited carcinoma growth and tumour progression both in vitro, in colorectal cancer cell lines, and in vivo, in a tumour xenograft mouse model, without apparent systemic toxicity in mice. Our results show for the first time that a small molecule putatively targeting the E3 ubiquitin-ligase Hakai inhibits Hakai-dependent ubiquitination of E-cadherin, having an impact on the EMT process. This represents an important step forward in a future development of an effective therapeutic drug to prevent or inhibit carcinoma tumour progression." @default.
- W3026177074 created "2020-05-29" @default.
- W3026177074 creator A5002183891 @default.
- W3026177074 creator A5029081977 @default.
- W3026177074 creator A5037980567 @default.
- W3026177074 creator A5045457074 @default.
- W3026177074 creator A5047935646 @default.
- W3026177074 creator A5048905988 @default.
- W3026177074 creator A5071957278 @default.
- W3026177074 creator A5082724722 @default.
- W3026177074 creator A5091401644 @default.
- W3026177074 date "2020-05-23" @default.
- W3026177074 modified "2023-10-16" @default.
- W3026177074 title "Hakin-1, a New Specific Small-Molecule Inhibitor for the E3 Ubiquitin-Ligase Hakai, Inhibits Carcinoma Growth and Progression" @default.
- W3026177074 cites W1744742580 @default.
- W3026177074 cites W1777707460 @default.
- W3026177074 cites W1794063461 @default.
- W3026177074 cites W1851733051 @default.
- W3026177074 cites W1966714888 @default.
- W3026177074 cites W1967945239 @default.
- W3026177074 cites W1968820967 @default.
- W3026177074 cites W1972076184 @default.
- W3026177074 cites W1979068418 @default.
- W3026177074 cites W1986476355 @default.
- W3026177074 cites W1987490729 @default.
- W3026177074 cites W1991841644 @default.
- W3026177074 cites W1995480433 @default.
- W3026177074 cites W2008273587 @default.
- W3026177074 cites W2016521092 @default.
- W3026177074 cites W2018468829 @default.
- W3026177074 cites W2023992908 @default.
- W3026177074 cites W2025647419 @default.
- W3026177074 cites W2032159017 @default.
- W3026177074 cites W2032930150 @default.
- W3026177074 cites W2033715459 @default.
- W3026177074 cites W2037554542 @default.
- W3026177074 cites W2047399603 @default.
- W3026177074 cites W2050182398 @default.
- W3026177074 cites W2051209842 @default.
- W3026177074 cites W2059830892 @default.
- W3026177074 cites W2069629727 @default.
- W3026177074 cites W2071374729 @default.
- W3026177074 cites W2074874387 @default.
- W3026177074 cites W2078364559 @default.
- W3026177074 cites W2087160148 @default.
- W3026177074 cites W2091597591 @default.
- W3026177074 cites W2097933346 @default.
- W3026177074 cites W2105372393 @default.
- W3026177074 cites W2107796582 @default.
- W3026177074 cites W2108235071 @default.
- W3026177074 cites W2114552883 @default.
- W3026177074 cites W2120163993 @default.
- W3026177074 cites W2122817748 @default.
- W3026177074 cites W2126166557 @default.
- W3026177074 cites W2134060226 @default.
- W3026177074 cites W2140399705 @default.
- W3026177074 cites W2144114582 @default.
- W3026177074 cites W2145932487 @default.
- W3026177074 cites W2147917253 @default.
- W3026177074 cites W2151224270 @default.
- W3026177074 cites W2155832320 @default.
- W3026177074 cites W2162488397 @default.
- W3026177074 cites W2164358503 @default.
- W3026177074 cites W2164879306 @default.
- W3026177074 cites W2183803121 @default.
- W3026177074 cites W2210282509 @default.
- W3026177074 cites W2264801869 @default.
- W3026177074 cites W2291567073 @default.
- W3026177074 cites W2310322011 @default.
- W3026177074 cites W2588238973 @default.
- W3026177074 cites W2621567555 @default.
- W3026177074 cites W2725141796 @default.
- W3026177074 cites W2758897789 @default.
- W3026177074 cites W2773382289 @default.
- W3026177074 cites W2775382512 @default.
- W3026177074 cites W2798231099 @default.
- W3026177074 cites W2805601712 @default.
- W3026177074 cites W2806918958 @default.
- W3026177074 cites W2884030111 @default.
- W3026177074 cites W2887314183 @default.
- W3026177074 cites W2906067435 @default.
- W3026177074 cites W3000207723 @default.
- W3026177074 cites W3016840787 @default.
- W3026177074 cites W4211233744 @default.
- W3026177074 doi "https://doi.org/10.3390/cancers12051340" @default.
- W3026177074 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7281109" @default.
- W3026177074 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32456234" @default.
- W3026177074 hasPublicationYear "2020" @default.
- W3026177074 type Work @default.
- W3026177074 sameAs 3026177074 @default.
- W3026177074 citedByCount "11" @default.
- W3026177074 countsByYear W30261770742020 @default.
- W3026177074 countsByYear W30261770742021 @default.
- W3026177074 countsByYear W30261770742022 @default.
- W3026177074 countsByYear W30261770742023 @default.
- W3026177074 crossrefType "journal-article" @default.
- W3026177074 hasAuthorship W3026177074A5002183891 @default.
- W3026177074 hasAuthorship W3026177074A5029081977 @default.