Loss of TRIM33 causes resistance to BET bromodomain inhibitors through MYC- and TGF-β–dependent mechanisms
Shi X, Mihaylova VT, Kuruvilla L, Chen F, Viviano S, Baldassarre M, Sperandio D, Martinez R, Yue P, Bates JG, Breckenridge DG, Schlessinger J, Turk BE, Calderwood DA. Loss of TRIM33 causes resistance to BET bromodomain inhibitors through MYC- and TGF-β–dependent mechanisms. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: e4558-e4566. PMID: 27432991, PMCID: PMC4978292, DOI: 10.1073/pnas.1608319113.Peer-Reviewed Original ResearchMeSH KeywordsAzepinesCell Line, TumorCell ProliferationColorectal NeoplasmsDrug ResistanceGene Expression Regulation, NeoplasticHCT116 CellsHEK293 CellsHumansMolecular StructureProteinsProto-Oncogene Proteins c-mycReceptors, Transforming Growth Factor betaRNA InterferenceSignal TransductionTranscription FactorsTransforming Growth Factor betaTriazolesConceptsTGF-β receptor activityExtraterminal domain protein inhibitorsRegulation of MYCCancer cellsBET bromodomain inhibitionShRNA screeningProtein 33TGF-β receptor expressionBromodomain inhibitorsProtein inhibitorInhibition of TGFColorectal cancer cellsBromodomain inhibitionBETi resistanceCancer therapeuticsNew therapeutic benefitsDurable responsesMYCDependent mechanismReceptor expressionTherapeutic benefitBETiReceptor activityResistant stateAntiproliferative effects