FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2046998382> ?p ?o ?g. }

• W2046998382 endingPage "863" @default.
• W2046998382 startingPage "857" @default.
• W2046998382 abstract "Abstract Her‐2/ neu ( erb B‐2) oncogene overexpression is associated with increased tumor progression and metastasis. Fatty acid synthase (FAS), the key lipogenic enzyme responsible for the endogenous synthesis of fatty acids, has been shown to be one of the genes regulated by Her‐2/ neu at the level of transcription, translation, and biosynthetic activity. Interestingly, we recently established that both pharmacological inhibition of FAS activity and silencing of FAS gene expression specifically suppress Her‐2/ neu oncoprotein expression and tyrosine‐kinase activity in breast and ovarian Her‐2/ neu overexpressors. Unraveling the functional organization of this novel bi‐directional molecular connection between Her‐2/ neu and FAS‐dependent neoplastic lipogenesis is a major challenge that the field is only beginning to take on. Considering that Her‐2/ neu overexpression correlates with increased expression of the hypoxia inducible factor‐1α (HIF‐1α), which, in a mitogen‐activated protein kinase (MAPK)‐dependent manner, plays a key role in the expression of several genes including cytokines such as vascular endothelial growth factor (VEGF), we hypothesized that FAS blockade should result in a concomitant down‐regulation of VEGF. Unexpectedly, the specific inhibition of the de novo fatty acid synthesis with the small‐molecule inhibitor of FAS activity C75 resulted in a dramatic dose‐dependent enhancement (up to 500% increase) of VEGF secretion in Her‐2/ neu ‐overexpressing SK‐Br3, BT‐474, and SKOV3 cancer cells. Concurrently, FAS blockade drastically activated MAPK and promoted further a prominent accumulation of HIF‐1α in Her‐2/ neu overexpressors. Moreover, U0126‐induced inhibition of MAPK activity completely abolished C75‐induced up‐regulation of HIF‐1α expression and VEGF secretion, whereas it did not modulate C75‐induced down‐regulation of Her‐2/ neu oncogene. Importantly, RNA interference (RNAi)‐mediated silencing of the FAS gene recapitulated C75's effects by up‐regulating VEGF secretion, MAPK activation and HIF‐1α expression. Therefore, it appears that perturbation of cancer‐associated endogenous fatty metabolism triggers a “hypoxia‐like” (oxygen‐independent) condition that actively rescues Her‐2/ neu ‐dependent MAPK → HIP‐1α → VEGF cascade. It is tempting to suggest that an intact FAS‐catalyzed endogenous fatty acid metabolism is a necessary metabolic adaptation to support the enhanced ability of Her‐2/ neu ‐overexpressing cancer cells to survive cellular hypoxia in a HIF‐α‐dependent manner. J. Cell. Biochem. 94: 857–863, 2005. © 2005 Wiley‐Liss, Inc." @default.
• W2046998382 created "2016-06-24" @default.
• W2046998382 creator A5012328790 @default.
• W2046998382 creator A5051386701 @default.
• W2046998382 creator A5077187730 @default.
• W2046998382 creator A5083270986 @default.
• W2046998382 date "2005-01-24" @default.
• W2046998382 modified "2023-10-11" @default.
• W2046998382 title "Does endogenous fatty acid metabolism allow cancer cells to sense hypoxia and mediate hypoxic vasodilatation? Characterization of a novel molecular connection between fatty acid synthase (FAS) and hypoxia-inducible factor-1? (HIF-1?)-related expression of vascular endothelial growth factor (VEGF) in cancer cells overexpressing her-2/neu oncogene" @default.
• W2046998382 cites W1508497000 @default.
• W2046998382 cites W1585199293 @default.
• W2046998382 cites W1830307401 @default.
• W2046998382 cites W1966823692 @default.
• W2046998382 cites W1972889113 @default.
• W2046998382 cites W1976608620 @default.
• W2046998382 cites W1983259239 @default.
• W2046998382 cites W2004427637 @default.
• W2046998382 cites W2011810742 @default.
• W2046998382 cites W2021422667 @default.
• W2046998382 cites W2024334459 @default.
• W2046998382 cites W2039731227 @default.
• W2046998382 cites W2043711125 @default.
• W2046998382 cites W2059010575 @default.
• W2046998382 cites W2059831744 @default.
• W2046998382 cites W2060041328 @default.
• W2046998382 cites W2066051514 @default.
• W2046998382 cites W2072227408 @default.
• W2046998382 cites W2093265805 @default.
• W2046998382 cites W2120807407 @default.
• W2046998382 cites W2141393790 @default.
• W2046998382 cites W2142786915 @default.
• W2046998382 cites W2147527625 @default.
• W2046998382 cites W2149456035 @default.
• W2046998382 cites W2159315949 @default.
• W2046998382 doi "https://doi.org/10.1002/jcb.20367" @default.
• W2046998382 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/15669079" @default.
• W2046998382 hasPublicationYear "2005" @default.
• W2046998382 type Work @default.
• W2046998382 sameAs 2046998382 @default.
• W2046998382 citedByCount "29" @default.
• W2046998382 countsByYear W20469983822012 @default.
• W2046998382 countsByYear W20469983822016 @default.
• W2046998382 countsByYear W20469983822017 @default.
• W2046998382 countsByYear W20469983822018 @default.
• W2046998382 countsByYear W20469983822019 @default.
• W2046998382 countsByYear W20469983822022 @default.
• W2046998382 crossrefType "journal-article" @default.
• W2046998382 hasAuthorship W2046998382A5012328790 @default.
• W2046998382 hasAuthorship W2046998382A5051386701 @default.
• W2046998382 hasAuthorship W2046998382A5077187730 @default.
• W2046998382 hasAuthorship W2046998382A5083270986 @default.
• W2046998382 hasConcept C104317684 @default.
• W2046998382 hasConcept C167734588 @default.
• W2046998382 hasConcept C184235292 @default.
• W2046998382 hasConcept C185592680 @default.
• W2046998382 hasConcept C22615655 @default.
• W2046998382 hasConcept C2777025900 @default.
• W2046998382 hasConcept C48289651 @default.
• W2046998382 hasConcept C502942594 @default.
• W2046998382 hasConcept C54009773 @default.
• W2046998382 hasConcept C543025807 @default.
• W2046998382 hasConcept C55493867 @default.
• W2046998382 hasConcept C57074206 @default.
• W2046998382 hasConcept C86339819 @default.
• W2046998382 hasConcept C86803240 @default.
• W2046998382 hasConcept C95444343 @default.
• W2046998382 hasConceptScore W2046998382C104317684 @default.
• W2046998382 hasConceptScore W2046998382C167734588 @default.
• W2046998382 hasConceptScore W2046998382C184235292 @default.
• W2046998382 hasConceptScore W2046998382C185592680 @default.
• W2046998382 hasConceptScore W2046998382C22615655 @default.
• W2046998382 hasConceptScore W2046998382C2777025900 @default.
• W2046998382 hasConceptScore W2046998382C48289651 @default.
• W2046998382 hasConceptScore W2046998382C502942594 @default.
• W2046998382 hasConceptScore W2046998382C54009773 @default.
• W2046998382 hasConceptScore W2046998382C543025807 @default.
• W2046998382 hasConceptScore W2046998382C55493867 @default.
• W2046998382 hasConceptScore W2046998382C57074206 @default.
• W2046998382 hasConceptScore W2046998382C86339819 @default.
• W2046998382 hasConceptScore W2046998382C86803240 @default.
• W2046998382 hasConceptScore W2046998382C95444343 @default.
• W2046998382 hasIssue "5" @default.
• W2046998382 hasLocation W20469983821 @default.
• W2046998382 hasLocation W20469983822 @default.
• W2046998382 hasOpenAccess W2046998382 @default.
• W2046998382 hasPrimaryLocation W20469983821 @default.
• W2046998382 hasRelatedWork W1497026393 @default.
• W2046998382 hasRelatedWork W1892260126 @default.
• W2046998382 hasRelatedWork W1927534900 @default.
• W2046998382 hasRelatedWork W2153033713 @default.
• W2046998382 hasRelatedWork W2316646634 @default.
• W2046998382 hasRelatedWork W2367468890 @default.
• W2046998382 hasRelatedWork W2952644164 @default.
• W2046998382 hasRelatedWork W3098534230 @default.
• W2046998382 hasRelatedWork W4210868349 @default.
• W2046998382 hasRelatedWork W4247413074 @default.
• W2046998382 hasVolume "94" @default.
• W2046998382 isParatext "false" @default.

• next