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dc.contributor.authorMandigo, AC
dc.contributor.authorYuan, W
dc.contributor.authorXu, K
dc.contributor.authorGallagher, P
dc.contributor.authorPang, A
dc.contributor.authorGuan, YF
dc.contributor.authorShafi, AA
dc.contributor.authorThangavel, C
dc.contributor.authorSheehan, B
dc.contributor.authorBogdan, D
dc.contributor.authorPaschalis, A
dc.contributor.authorMcCann, JJ
dc.contributor.authorLaufer, TS
dc.contributor.authorGordon, N
dc.contributor.authorVasilevskaya, IA
dc.contributor.authorDylgjeri, E
dc.contributor.authorChand, SN
dc.contributor.authorSchiewer, MJ
dc.contributor.authorDomingo-Domenech, J
dc.contributor.authorDen, RB
dc.contributor.authorHolst, J
dc.contributor.authorMcCue, PA
dc.contributor.authorde Bono, JS
dc.contributor.authorMcNair, C
dc.contributor.authorKnudsen, KE
dc.date.accessioned2021-06-11T13:07:11Z
dc.date.available2021-06-11T13:07:11Z
dc.date.issued2021-04-20
dc.identifier.citationCancer discovery, 2021en_US
dc.identifier.issn2159-8274
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4635
dc.identifier.eissn2159-8290en_US
dc.identifier.eissn2159-8290
dc.identifier.doi10.1158/2159-8290.cd-20-1114en_US
dc.identifier.doi10.1158/2159-8290.cd-20-1114
dc.description.abstractLoss of the retinoblastoma (RB) tumor suppressor protein is a critical step in reprogramming biological networks that drive cancer progression, although mechanistic insight has been largely limited to the impact of RB loss on cell cycle regulation. Here, isogenic modeling of RB loss identified disease stage-specific rewiring of E2F1 function, providing the first-in-field mapping of the E2F1 cistrome and transcriptome after RB loss across disease progression. Biochemical and functional assessment using both in vitro and in vivo models identified an unexpected, prominent role for E2F1 in regulation of redox metabolism after RB loss, driving an increase in the synthesis of the antioxidant, glutathione, specific to advanced disease. These E2F1-dependent events resulted in protection from reactive oxygen species (ROS) in response to therapeutic intervention. On balance, these findings reveal novel pathways through which RB loss promotes cancer progression and highlight potentially new nodes of intervention for treating RB-deficient cancers.en_US
dc.formatPrint-Electronicen_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://www.rioxx.net/licenses/all-rights-reserveden_US
dc.titleRB/E2F1 as a master regulator of cancer cell metabolism in advanced disease.en_US
dc.typeJournal Article
dcterms.dateAccepted2021-04-16
rioxxterms.versionVoRen_US
rioxxterms.versionofrecord10.1158/2159-8290.cd-20-1114en_US
rioxxterms.licenseref.startdate2021-04-20
dc.relation.isPartOfCancer discoveryen_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group
pubs.publication-statusPublisheden_US
pubs.embargo.termsNot knownen_US
icr.researchteamProstate Cancer Targeted Therapy Group
dc.contributor.icrauthorDe Bono, Johannen_US


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