Matches in SemOpenAlex for { <https://semopenalex.org/work/W2008777301> ?p ?o ?g. }
- W2008777301 endingPage "114" @default.
- W2008777301 startingPage "110" @default.
- W2008777301 abstract "Mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 are among the most common genetic alterations in intrahepatic cholangiocarcinoma (IHCC), a deadly liver cancer. Mutant IDH proteins in IHCC and other malignancies acquire an abnormal enzymatic activity allowing them to convert α-ketoglutarate (αKG) to 2-hydroxyglutarate (2HG), which inhibits the activity of multiple αKG-dependent dioxygenases, and results in alterations in cell differentiation, survival, and extracellular matrix maturation. However, the molecular pathways by which IDH mutations lead to tumour formation remain unclear. Here we show that mutant IDH blocks liver progenitor cells from undergoing hepatocyte differentiation through the production of 2HG and suppression of HNF-4α, a master regulator of hepatocyte identity and quiescence. Correspondingly, genetically engineered mouse models expressing mutant IDH in the adult liver show an aberrant response to hepatic injury, characterized by HNF-4α silencing, impaired hepatocyte differentiation, and markedly elevated levels of cell proliferation. Moreover, IDH and Kras mutations, genetic alterations that co-exist in a subset of human IHCCs, cooperate to drive the expansion of liver progenitor cells, development of premalignant biliary lesions, and progression to metastatic IHCC. These studies provide a functional link between IDH mutations, hepatic cell fate, and IHCC pathogenesis, and present a novel genetically engineered mouse model of IDH-driven malignancy." @default.
- W2008777301 created "2016-06-24" @default.
- W2008777301 creator A5004285957 @default.
- W2008777301 creator A5005813857 @default.
- W2008777301 creator A5007574547 @default.
- W2008777301 creator A5009207051 @default.
- W2008777301 creator A5012107830 @default.
- W2008777301 creator A5013982237 @default.
- W2008777301 creator A5019034689 @default.
- W2008777301 creator A5021050825 @default.
- W2008777301 creator A5022001224 @default.
- W2008777301 creator A5025457807 @default.
- W2008777301 creator A5026365081 @default.
- W2008777301 creator A5027070774 @default.
- W2008777301 creator A5032742387 @default.
- W2008777301 creator A5036625904 @default.
- W2008777301 creator A5038367858 @default.
- W2008777301 creator A5038972103 @default.
- W2008777301 creator A5041719692 @default.
- W2008777301 creator A5048559395 @default.
- W2008777301 creator A5050943295 @default.
- W2008777301 creator A5052975894 @default.
- W2008777301 creator A5053897548 @default.
- W2008777301 creator A5061627885 @default.
- W2008777301 creator A5064406116 @default.
- W2008777301 creator A5076775286 @default.
- W2008777301 creator A5077924099 @default.
- W2008777301 creator A5088566246 @default.
- W2008777301 date "2014-07-02" @default.
- W2008777301 modified "2023-10-18" @default.
- W2008777301 title "Mutant IDH inhibits HNF-4α to block hepatocyte differentiation and promote biliary cancer" @default.
- W2008777301 cites W1255676896 @default.
- W2008777301 cites W1593612940 @default.
- W2008777301 cites W1918772537 @default.
- W2008777301 cites W1975667412 @default.
- W2008777301 cites W1976199077 @default.
- W2008777301 cites W1977859620 @default.
- W2008777301 cites W1979728979 @default.
- W2008777301 cites W1982953415 @default.
- W2008777301 cites W1982959726 @default.
- W2008777301 cites W1985342348 @default.
- W2008777301 cites W1988559329 @default.
- W2008777301 cites W2001008402 @default.
- W2008777301 cites W2007832228 @default.
- W2008777301 cites W2009550277 @default.
- W2008777301 cites W2014297339 @default.
- W2008777301 cites W2016456139 @default.
- W2008777301 cites W2018041848 @default.
- W2008777301 cites W2018051392 @default.
- W2008777301 cites W2023723464 @default.
- W2008777301 cites W2031073046 @default.
- W2008777301 cites W2035409103 @default.
- W2008777301 cites W2050178904 @default.
- W2008777301 cites W2052790535 @default.
- W2008777301 cites W2053483691 @default.
- W2008777301 cites W2080452140 @default.
- W2008777301 cites W2084074847 @default.
- W2008777301 cites W2096796171 @default.
- W2008777301 cites W2099755414 @default.
- W2008777301 cites W2101974070 @default.
- W2008777301 cites W2112495947 @default.
- W2008777301 cites W2131241595 @default.
- W2008777301 cites W2131860315 @default.
- W2008777301 cites W2141750100 @default.
- W2008777301 cites W2154313451 @default.
- W2008777301 cites W2154649976 @default.
- W2008777301 cites W2162619595 @default.
- W2008777301 cites W2164219809 @default.
- W2008777301 cites W4211025847 @default.
- W2008777301 doi "https://doi.org/10.1038/nature13441" @default.
- W2008777301 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4499230" @default.
- W2008777301 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25043045" @default.
- W2008777301 hasPublicationYear "2014" @default.
- W2008777301 type Work @default.
- W2008777301 sameAs 2008777301 @default.
- W2008777301 citedByCount "345" @default.
- W2008777301 countsByYear W20087773012014 @default.
- W2008777301 countsByYear W20087773012015 @default.
- W2008777301 countsByYear W20087773012016 @default.
- W2008777301 countsByYear W20087773012017 @default.
- W2008777301 countsByYear W20087773012018 @default.
- W2008777301 countsByYear W20087773012019 @default.
- W2008777301 countsByYear W20087773012020 @default.
- W2008777301 countsByYear W20087773012021 @default.
- W2008777301 countsByYear W20087773012022 @default.
- W2008777301 countsByYear W20087773012023 @default.
- W2008777301 crossrefType "journal-article" @default.
- W2008777301 hasAuthorship W2008777301A5004285957 @default.
- W2008777301 hasAuthorship W2008777301A5005813857 @default.
- W2008777301 hasAuthorship W2008777301A5007574547 @default.
- W2008777301 hasAuthorship W2008777301A5009207051 @default.
- W2008777301 hasAuthorship W2008777301A5012107830 @default.
- W2008777301 hasAuthorship W2008777301A5013982237 @default.
- W2008777301 hasAuthorship W2008777301A5019034689 @default.
- W2008777301 hasAuthorship W2008777301A5021050825 @default.
- W2008777301 hasAuthorship W2008777301A5022001224 @default.
- W2008777301 hasAuthorship W2008777301A5025457807 @default.
- W2008777301 hasAuthorship W2008777301A5026365081 @default.