Matches in SemOpenAlex for { <https://semopenalex.org/work/W2116711289> ?p ?o ?g. }
- W2116711289 endingPage "9165" @default.
- W2116711289 startingPage "9153" @default.
- W2116711289 abstract "Abstract Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is caused by mutations in the Krebs cycle enzyme fumarate hydratase (FH). It has been proposed that “pseudohypoxic” stabilization of hypoxia-inducible factor-α (HIF-α) by fumarate accumulation contributes to tumorigenesis in HLRCC. We hypothesized that an additional direct consequence of FH deficiency is the establishment of a biosynthetic milieu. To investigate this hypothesis, we isolated primary mouse embryonic fibroblast (MEF) lines from Fh1-deficient mice. As predicted, these MEFs upregulated Hif-1α and HIF target genes directly as a result of FH deficiency. In addition, detailed metabolic assessment of these MEFs confirmed their dependence on glycolysis, and an elevated rate of lactate efflux, associated with the upregulation of glycolytic enzymes known to be associated with tumorigenesis. Correspondingly, Fh1-deficient benign murine renal cysts and an advanced human HLRCC-related renal cell carcinoma manifested a prominent and progressive increase in the expression of HIF-α target genes and in genes known to be relevant to tumorigenesis and metastasis. In accord with our hypothesis, in a variety of different FH-deficient tissues, including a novel murine model of Fh1-deficient smooth muscle, we show a striking and progressive upregulation of a tumorigenic metabolic profile, as manifested by increased PKM2 and LDHA protein. Based on the models assessed herein, we infer that that FH deficiency compels cells to adopt an early, reversible, and progressive protumorigenic metabolic milieu that is reminiscent of that driving the Warburg effect. Targets identified in these novel and diverse FH-deficient models represent excellent potential candidates for further mechanistic investigation and therapeutic metabolic manipulation in tumors. Cancer Res; 70(22); 9153–65. ©2010 AACR." @default.
- W2116711289 created "2016-06-24" @default.
- W2116711289 creator A5000702424 @default.
- W2116711289 creator A5007935219 @default.
- W2116711289 creator A5020572950 @default.
- W2116711289 creator A5021869565 @default.
- W2116711289 creator A5023214669 @default.
- W2116711289 creator A5023595055 @default.
- W2116711289 creator A5028725974 @default.
- W2116711289 creator A5029547604 @default.
- W2116711289 creator A5034095842 @default.
- W2116711289 creator A5036143326 @default.
- W2116711289 creator A5036177265 @default.
- W2116711289 creator A5036848232 @default.
- W2116711289 creator A5040598662 @default.
- W2116711289 creator A5043932592 @default.
- W2116711289 creator A5046830436 @default.
- W2116711289 creator A5052921186 @default.
- W2116711289 creator A5053242056 @default.
- W2116711289 creator A5054187545 @default.
- W2116711289 creator A5055014981 @default.
- W2116711289 creator A5059084742 @default.
- W2116711289 creator A5061361347 @default.
- W2116711289 creator A5062350441 @default.
- W2116711289 creator A5064124314 @default.
- W2116711289 creator A5067455165 @default.
- W2116711289 creator A5071077684 @default.
- W2116711289 creator A5071837807 @default.
- W2116711289 creator A5071912561 @default.
- W2116711289 creator A5072503541 @default.
- W2116711289 creator A5073711542 @default.
- W2116711289 creator A5082162425 @default.
- W2116711289 creator A5088612483 @default.
- W2116711289 date "2010-11-14" @default.
- W2116711289 modified "2023-10-18" @default.
- W2116711289 title "Expression Profiling in Progressive Stages of Fumarate-Hydratase Deficiency: The Contribution of Metabolic Changes to Tumorigenesis" @default.
- W2116711289 cites W1913707124 @default.
- W2116711289 cites W1963933525 @default.
- W2116711289 cites W1966133093 @default.
- W2116711289 cites W1967291345 @default.
- W2116711289 cites W1967990571 @default.
- W2116711289 cites W1971568000 @default.
- W2116711289 cites W1984021937 @default.
- W2116711289 cites W1984485637 @default.
- W2116711289 cites W1988377666 @default.
- W2116711289 cites W2002816359 @default.
- W2116711289 cites W2004056464 @default.
- W2116711289 cites W2004183689 @default.
- W2116711289 cites W2007012192 @default.
- W2116711289 cites W2015207840 @default.
- W2116711289 cites W2028117213 @default.
- W2116711289 cites W2029023103 @default.
- W2116711289 cites W2037632318 @default.
- W2116711289 cites W2040908275 @default.
- W2116711289 cites W2043034889 @default.
- W2116711289 cites W2046424783 @default.
- W2116711289 cites W2048255587 @default.
- W2116711289 cites W2057199368 @default.
- W2116711289 cites W2058691572 @default.
- W2116711289 cites W2059747280 @default.
- W2116711289 cites W2060525294 @default.
- W2116711289 cites W2074820129 @default.
- W2116711289 cites W2076057425 @default.
- W2116711289 cites W2085207827 @default.
- W2116711289 cites W2097259163 @default.
- W2116711289 cites W2098189012 @default.
- W2116711289 cites W2105250121 @default.
- W2116711289 cites W2108346377 @default.
- W2116711289 cites W2110251906 @default.
- W2116711289 cites W2112738731 @default.
- W2116711289 cites W2113945778 @default.
- W2116711289 cites W2120370940 @default.
- W2116711289 cites W2125955965 @default.
- W2116711289 cites W2126817554 @default.
- W2116711289 cites W2130265677 @default.
- W2116711289 cites W2131964237 @default.
- W2116711289 cites W2136729555 @default.
- W2116711289 cites W2136749294 @default.
- W2116711289 cites W2137960344 @default.
- W2116711289 cites W2141063928 @default.
- W2116711289 cites W2141278789 @default.
- W2116711289 cites W2160896252 @default.
- W2116711289 cites W2162262059 @default.
- W2116711289 cites W2163239105 @default.
- W2116711289 cites W2168611920 @default.
- W2116711289 cites W2170526668 @default.
- W2116711289 doi "https://doi.org/10.1158/0008-5472.can-10-1949" @default.
- W2116711289 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20978192" @default.
- W2116711289 hasPublicationYear "2010" @default.
- W2116711289 type Work @default.
- W2116711289 sameAs 2116711289 @default.
- W2116711289 citedByCount "60" @default.
- W2116711289 countsByYear W21167112892012 @default.
- W2116711289 countsByYear W21167112892013 @default.
- W2116711289 countsByYear W21167112892014 @default.
- W2116711289 countsByYear W21167112892015 @default.
- W2116711289 countsByYear W21167112892016 @default.
- W2116711289 countsByYear W21167112892017 @default.