2024
BET degrader exhibits lower antiproliferative activity than its inhibitor via EGR1 recruiting septins to promote E2F1-3 transcription in triple-negative breast cancer
Liu N, Wang S, Li M, Zhao N, Wang D, Zhang R, Yu M, Zhao L, Zhang S, Han F, Zhao Y, Liu Q. BET degrader exhibits lower antiproliferative activity than its inhibitor via EGR1 recruiting septins to promote E2F1-3 transcription in triple-negative breast cancer. Pharmacological Research 2024, 208: 107377. PMID: 39209080, DOI: 10.1016/j.phrs.2024.107377.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsBromodomain Containing ProteinsCell Cycle ProteinsCell Line, TumorCell ProliferationE2F Transcription FactorsE2F1 Transcription FactorE2F3 Transcription FactorEarly Growth Response Protein 1FemaleGene Expression Regulation, NeoplasticHumansMediator Complex Subunit 1MiceMice, NudeTranscription FactorsTranscription, GeneticTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerBET proteinsRNA polymerase IIBET bromodomainsInhibiting BET proteinsInhibition of cell growthBET degradersBreast cancerPolymerase IIFamily proteinsCell proliferation rate in vitroIncreased Egr1 expressionProliferation rate in vitroBRD4 depletionLysine residuesSeptinE2F1Cell growthRate in vitroExtraterminal domainAntiproliferative activityBET inhibitionProteinEGR1 expressionCell proliferation
2022
BRD4 inhibitor suppresses melanoma metastasis via the SPINK6/EGFR-EphA2 pathway
Hu R, Li Y, Guo Y, Li X, Du S, Liao M, Hou H, Sun H, Zhao S, Su J, Chen X, Yin M. BRD4 inhibitor suppresses melanoma metastasis via the SPINK6/EGFR-EphA2 pathway. Pharmacological Research 2022, 187: 106609. PMID: 36516883, DOI: 10.1016/j.phrs.2022.106609.Peer-Reviewed Original ResearchChromatin Rewiring by Mismatch Repair Protein MSH2 Alters Cell Adhesion Pathways and Sensitivity to BET Inhibition in Gastric Cancer.
Nargund A, Xu C, Mandoli A, Okabe A, Chen G, Huang K, Sheng T, Yao X, Teo J, Sundar R, Kok Y, See Y, Xing M, Li Z, Yong C, Anand A, Bin Adam Isa Z, Poon L, Ng M, Koh J, Ooi W, Tay S, Ong X, Tan A, Smoot D, Ashktorab H, Grabsch H, Fullwood M, Teh B, Bi X, Kaneda A, Li S, Tan P. Chromatin Rewiring by Mismatch Repair Protein MSH2 Alters Cell Adhesion Pathways and Sensitivity to BET Inhibition in Gastric Cancer. Cancer Research 2022, 82: 2538-2551. PMID: 35583999, DOI: 10.1158/0008-5472.can-21-2072.Peer-Reviewed Original ResearchConceptsEnhancer-promoter interactionsCell adhesion genesGenomic bindingAdhesion genesExpression of cell adhesion genesPathway expressionBET inhibitionCell adhesion pathwaysFunction of MSH2DNA mismatch repair genes MSH2Mismatch repair genes MSH2Sensitivity to BET inhibitionTumorigenesis in vitroHistone acetylation levelsChromatin rewiringChromatin functionEpigenomic functionsDNA repair genesSuper-enhancersGene locusEpigenomic regulationFunctional screeningSynthetic lethalityDNA repairAdhesion pathways
2021
Super enhancer regulation of cytokine-induced chemokine production in alcoholic hepatitis
Liu M, Cao S, He L, Gao J, Arab J, Cui H, Xuan W, Gao Y, Sehrawat T, Hamdan F, Ventura-Cots M, Argemi J, Pomerantz W, Johnsen S, Lee J, Gao F, Ordog T, Mathurin P, Revzin A, Bataller R, Yan H, Shah V. Super enhancer regulation of cytokine-induced chemokine production in alcoholic hepatitis. Nature Communications 2021, 12: 4560. PMID: 34315876, PMCID: PMC8316465, DOI: 10.1038/s41467-021-24843-w.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsChemokinesCytokinesDisease Models, AnimalEndothelial CellsEnhancer Elements, GeneticEpigenesis, GeneticGene Expression RegulationHepatitis, AlcoholicHistonesHumansLipopolysaccharidesLiverMice, Inbred C57BLNeutrophilsNF-kappa BPromoter Regions, GeneticRNA-SeqSignal TransductionTranscription FactorsTumor Necrosis Factor-alphaConceptsAlcoholic hepatitisLiver sinusoidal endothelial cellsChemokine expressionNeutrophil infiltrationLiver neutrophil infiltrationTNFα/NF-κB signalingNF-κB signalingHuman liver explantsElevated chemokine expressionSinusoidal endothelial cellsCXCL expressionChemokine productionCXCL chemokinesCytokine pathwaysCytokines TNFαInflammatory signalingMurine modelLiver explantsTherapeutic potentialPharmacologic inhibitionExtraterminal (BET) proteinsBET inhibitionHuman liverEndothelial cellsAH treatment
2018
Overcoming Resistance to Dual Innate Immune and MEK Inhibition Downstream of KRAS
Kitajima S, Asahina H, Chen T, Guo S, Quiceno L, Cavanaugh J, Merlino A, Tange S, Terai H, Kim J, Wang X, Zhou S, Xu M, Wang S, Zhu Z, Thai T, Takahashi C, Wang Y, Neve R, Stinson S, Tamayo P, Watanabe H, Kirschmeier P, Wong K, Barbie D. Overcoming Resistance to Dual Innate Immune and MEK Inhibition Downstream of KRAS. Cancer Cell 2018, 34: 439-452.e6. PMID: 30205046, PMCID: PMC6422029, DOI: 10.1016/j.ccell.2018.08.009.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAMP-Activated Protein Kinase KinasesAMP-Activated Protein KinasesAnimalsAntineoplastic Agents, ImmunologicalCarcinoma, Non-Small-Cell LungCell Line, TumorDisease Models, AnimalDrug Resistance, NeoplasmHEK293 CellsHumansImmunity, InnateInsulin-Like Growth Factor ILung NeoplasmsMiceMice, TransgenicMitogen-Activated Protein Kinase KinasesPhosphoproteinsProtein Kinase InhibitorsProtein Serine-Threonine KinasesProto-Oncogene Proteins p21(ras)Transcription FactorsYAP-Signaling ProteinsConceptsGenetically engineered mouse modelsMediators of acquired resistanceDownstream of KRASBET inhibitor JQ1Effective therapeutic strategyTumor shrinkageTargeted therapyIntermittent treatmentYAP1 signalingMouse modelPathway inhibitionBET inhibitionTherapeutic strategiesInhibitor JQ1YAP1 upregulationOncogenic KrasBET inhibitorsOvercome resistancePromoter acetylationIntrinsic resistancePotential translationKRASMEKInnateInhibitionBET inhibition in advanced cutaneous T cell lymphoma is synergistically potentiated by BCL2 inhibition or HDAC inhibition
Kim R, Lewis JM, Cyrenne BM, Monico PF, Mirza FN, Carlson KR, Foss FM, Girardi M. BET inhibition in advanced cutaneous T cell lymphoma is synergistically potentiated by BCL2 inhibition or HDAC inhibition. Oncotarget 2018, 9: 29193-29207. PMID: 30018745, PMCID: PMC6044378, DOI: 10.18632/oncotarget.25670.Peer-Reviewed Original ResearchCutaneous T-cell lymphomaT-cell lymphomaCTCL cellsBCL2 inhibitionCell lymphomaAdvanced cutaneous T-cell lymphomaHDAC inhibitionSkin-homing T cellsPromising novel therapeutic strategyBET inhibitionNon-Hodgkin lymphomaPotential novel therapyCTCL cell linesDose-dependent decreaseNovel therapeutic strategiesHistone deacetylase inhibitionExtraterminal protein inhibitorSystemic therapyLymph nodesPeripheral bloodNovel therapiesT cellsTherapeutic strategiesCaspase-3/7 activationAdvanced stage
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