Please use this identifier to cite or link to this item: http://hdl.handle.net/1822/62002

Full metadata record
DC FieldValueLanguage
dc.contributor.authorZecchini, Vincentpor
dc.contributor.authorMadhu, Basettipor
dc.contributor.authorRussell, Roslinpor
dc.contributor.authorPértega-Gomes, Nelmapor
dc.contributor.authorWarren, Annepor
dc.contributor.authorGaude, Edoardopor
dc.contributor.authorBorlido, Joanapor
dc.contributor.authorStark, Rorypor
dc.contributor.authorIreland-Zecchini, Heatherpor
dc.contributor.authorRao, Roheetpor
dc.contributor.authorScott, Helenpor
dc.contributor.authorBoren, Joanpor
dc.contributor.authorMassie, Charliepor
dc.contributor.authorAsim, Mohammadpor
dc.contributor.authorBrindle, Kevinpor
dc.contributor.authorGriffiths, Johnpor
dc.contributor.authorFrezza, Christianpor
dc.contributor.authorNeal, David E.por
dc.contributor.authorMills, Ian G.por
dc.date.accessioned2019-11-08T17:18:03Z-
dc.date.issued2014-06-17-
dc.identifier.citationZecchini, V., Madhu, B., Russell, R., Pértega‐Gomes, N., et. al. (2014). Nuclear ARRB1 induces pseudohypoxia and cellular metabolism reprogramming in prostate cancer. The EMBO journal, 33(12), 1365-1382.por
dc.identifier.issn0261-4189-
dc.identifier.urihttp://hdl.handle.net/1822/62002-
dc.description.abstractTumour cells sustain their high proliferation rate through metabolic reprogramming, whereby cellular metabolism shifts from oxidative phosphorylation to aerobic glycolysis, even under normal oxygen levels. Hypoxia-inducible factor 1A (HIF1A) is a major regulator of this process, but its activation under normoxic conditions, termed pseudohypoxia, is not well documented. Here, using an integrative approach combining the first genome-wide mapping of chromatin binding for an endocytic adaptor, ARRB1, both in vitro and in vivo with gene expression profiling, we demonstrate that nuclear ARRB1 contributes to this metabolic shift in prostate cancer cells via regulation of HIF1A transcriptional activity under normoxic conditions through regulation of succinate dehydrogenase A (SDHA) and fumarate hydratase (FH) expression. ARRB1-induced pseudohypoxia may facilitate adaptation of cancer cells to growth in the harsh conditions that are frequently encountered within solid tumours. Our study is the first example of an endocytic adaptor protein regulating metabolic pathways. It implicates ARRB1 as a potential tumour promoter in prostate cancer and highlights the importance of metabolic alterations in prostate cancer.por
dc.language.isoengpor
dc.publisherEMBOpor
dc.rightsrestrictedAccesspor
dc.subjectArrestinspor
dc.subjectChromatin Immunoprecipitationpor
dc.subjectFluorescent Antibody Techniquepor
dc.subjectFumarate Hydratasepor
dc.subjectGas Chromatography-Mass Spectrometrypor
dc.subjectGene Expression Profilingpor
dc.subjectHumanspor
dc.subjectHypoxia-Inducible Factor 1, alpha Subunitpor
dc.subjectImmunoblottingpor
dc.subjectImmunohistochemistrypor
dc.subjectMagnetic Resonance Spectroscopypor
dc.subjectMalepor
dc.subjectMetabolic Networks and Pathwayspor
dc.subjectMetabolomicspor
dc.subjectProstatic Neoplasmspor
dc.subjectRNA Interferencepor
dc.subjectSuccinate Dehydrogenasepor
dc.subjectTissue Array Analysispor
dc.subjectbeta-Arrestin 1por
dc.subjectbeta-Arrestinspor
dc.subjectModels, Biologicalpor
dc.subjectAdaptorpor
dc.subjecthypoxiapor
dc.subjectmetabolismpor
dc.subjectprostatepor
dc.subjecttranscriptionpor
dc.titleNuclear ARRB1 induces pseudohypoxia and cellular metabolism reprogramming in prostate cancerpor
dc.typearticlepor
dc.peerreviewedyespor
dc.relation.publisherversionhttps://www.embopress.org/doi/full/10.15252/embj.201386874por
oaire.citationStartPage1365por
oaire.citationEndPage1382por
oaire.citationIssue12por
oaire.citationVolume33por
dc.identifier.essn1460-2075-
dc.identifier.doi10.15252/embj.201386874por
dc.date.embargo10000-01-01-
dc.identifier.pmid24837709por
dc.subject.fosCiências Médicas::Medicina Básicapor
dc.subject.wosScience & Technologypor
sdum.journalEmbo Journalpor
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

Files in This Item:
File Description SizeFormat 
Zecchini-2014-Nuclear-arrb-induces-pseudohypoxia-.pdf
  Restricted access
3 MBAdobe PDFView/Open

Partilhe no FacebookPartilhe no TwitterPartilhe no DeliciousPartilhe no LinkedInPartilhe no DiggAdicionar ao Google BookmarksPartilhe no MySpacePartilhe no Orkut
Exporte no formato BibTex mendeley Exporte no formato Endnote Adicione ao seu ORCID