Featured Publications
CECR2 drives breast cancer metastasis by promoting NF-κB signaling and macrophage-mediated immune suppression
Zhang M, Liu ZZ, Aoshima K, Cai WL, Sun H, Xu T, Zhang Y, An Y, Chen JF, Chan LH, Aoshima A, Lang SM, Tang Z, Che X, Li Y, Rutter SJ, Bossuyt V, Chen X, Morrow JS, Pusztai L, Rimm DL, Yin M, Yan Q. CECR2 drives breast cancer metastasis by promoting NF-κB signaling and macrophage-mediated immune suppression. Science Translational Medicine 2022, 14: eabf5473. PMID: 35108062, PMCID: PMC9003667, DOI: 10.1126/scitranslmed.abf5473.Peer-Reviewed Original ResearchConceptsBreast cancer metastasisReticuloendotheliosis viral oncogene homolog ACancer metastasisImmune suppressionM2 macrophagesWorse metastasis-free survivalMetastatic breast cancerMetastasis-free survivalV-rel avian reticuloendotheliosis viral oncogene homolog ACancer-related deathPrimary breast tumorsMultiple mouse modelsNF-κB signalingImmunocompetent settingNuclear factor-κB family membersMetastasis-promoting genesDistant metastasisMetastatic sitesPrimary tumorEffective therapyBreast cancerMetastasis treatmentMouse modelBreast tumorsMetastasisPotent BRD4 inhibitor suppresses cancer cell-macrophage interaction
Yin M, Guo Y, Hu R, Cai WL, Li Y, Pei S, Sun H, Peng C, Li J, Ye R, Yang Q, Wang N, Tao Y, Chen X, Yan Q. Potent BRD4 inhibitor suppresses cancer cell-macrophage interaction. Nature Communications 2020, 11: 1833. PMID: 32286255, PMCID: PMC7156724, DOI: 10.1038/s41467-020-15290-0.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAnimalsCell CommunicationCell Cycle ProteinsCell Line, TumorCell ProliferationDisease Models, AnimalDown-RegulationDrug DesignFemaleHumansHypoxia-Inducible Factor 1, alpha SubunitMacrophage Colony-Stimulating FactorMacrophagesMice, Inbred BALB CMice, NudeNeoplasmsPhosphorylationProto-Oncogene Proteins c-mycReceptors, Granulocyte-Macrophage Colony-Stimulating FactorSignal TransductionTranscription FactorsTreatment OutcomeConceptsTumor growthMajor clinical stagesBET inhibitorsProliferation of tumorsExtraterminal domain (BET) family proteinsTumor cell proliferationClinical stageTumor shrinkageSyngeneic modelPotent BRD4 inhibitorsSmall molecule inhibitorsSolid tumorsBRD4 inhibitionTumor cellsOral bioavailabilityCancer treatmentCell proliferationBRD4 inhibitorsMolecule inhibitorsMultiple mechanismsC-MycTumorsInhibitors
2024
Combined BET and MEK Inhibition synergistically suppresses melanoma by targeting YAP1
Hu R, Hou H, Li Y, Zhang M, Li X, Chen Y, Guo Y, Sun H, Zhao S, Liao M, Cao D, Yan Q, Chen X, Yin M. Combined BET and MEK Inhibition synergistically suppresses melanoma by targeting YAP1. Theranostics 2024, 14: 593-607. PMID: 38169595, PMCID: PMC10758063, DOI: 10.7150/thno.85437.Peer-Reviewed Original ResearchConceptsMEK inhibitor resistanceMEK inhibitor trametinibTrametinib treatmentInhibitor resistanceInhibitor trametinibMelanoma patientsYAP1 expressionMEK inhibitionBRAF-mutant melanoma patientsResistance to MEK inhibitionYAP1 inhibitionResistance to trametinibMelanoma growth <i>inInhibition of BRD4Trametinib resistanceAntitumor effectMelanoma growthTrametinibNHWD-870YAP1 inhibitorDrug resistanceMelanomaMelanoma samplesMelanoma cellsBRD4 depletion
2023
Mammalian SWI/SNF chromatin remodeling complexes promote tyrosine kinase inhibitor resistance in EGFR-mutant lung cancer
de Miguel F, Gentile C, Feng W, Silva S, Sankar A, Exposito F, Cai W, Melnick M, Robles-Oteiza C, Hinkley M, Tsai J, Hartley A, Wei J, Wurtz A, Li F, Toki M, Rimm D, Homer R, Wilen C, Xiao A, Qi J, Yan Q, Nguyen D, Jänne P, Kadoch C, Politi K. Mammalian SWI/SNF chromatin remodeling complexes promote tyrosine kinase inhibitor resistance in EGFR-mutant lung cancer. Cancer Cell 2023, 41: 1516-1534.e9. PMID: 37541244, PMCID: PMC10957226, DOI: 10.1016/j.ccell.2023.07.005.Peer-Reviewed Original ResearchConceptsMammalian SWI/SNF chromatinSWI/SNF chromatinMSWI/SNF complexesGenome-wide localizationGene regulatory signaturesNon-genetic mechanismsEpithelial cell differentiationEGFR-mutant cellsChromatin accessibilitySNF complexCellular programsRegulatory signaturesTKI-resistant lung cancerGene targetsKinase inhibitor resistanceCell differentiationMesenchymal transitionTKI resistancePharmacologic disruptionTyrosine kinase inhibitor resistanceCell proliferationChromatinInhibitor resistanceEGFR-mutant lungKinase inhibitorsPharmacological disruption of mSWI/SNF complex activity restricts SARS-CoV-2 infection
Wei J, Patil A, Collings C, Alfajaro M, Liang Y, Cai W, Strine M, Filler R, DeWeirdt P, Hanna R, Menasche B, Ökten A, Peña-Hernández M, Klein J, McNamara A, Rosales R, McGovern B, Luis Rodriguez M, García-Sastre A, White K, Qin Y, Doench J, Yan Q, Iwasaki A, Zwaka T, Qi J, Kadoch C, Wilen C. Pharmacological disruption of mSWI/SNF complex activity restricts SARS-CoV-2 infection. Nature Genetics 2023, 55: 471-483. PMID: 36894709, PMCID: PMC10011139, DOI: 10.1038/s41588-023-01307-z.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin-Converting Enzyme 2ChromatinCOVID-19DNA HelicasesHumansNuclear ProteinsSARS-CoV-2Transcription FactorsConceptsMSWI/SNF complexesAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionHost-directed therapeutic targetSyndrome coronavirus 2 infectionSARS-CoV-2 infectionSWItch/Sucrose Non-Fermentable (SWI/SNF) chromatinSARS-CoV-2 susceptibilityNon-fermentable (SWI/SNF) chromatinCoronavirus 2 infectionEnzyme 2 (ACE2) expressionSARS-CoV-2 variantsHuman cell typesPrimary human cell typesAirway epithelial cellsDrug-resistant variantsNew drug targetsChromatin accessibilitySNF complexACE2 locusACE2 expressionFactor complexHost determinantsTherapeutic targetConfer resistance
2022
Integrative molecular and clinical profiling of acral melanoma links focal amplification of 22q11.21 to metastasis
Farshidfar F, Rhrissorrakrai K, Levovitz C, Peng C, Knight J, Bacchiocchi A, Su J, Yin M, Sznol M, Ariyan S, Clune J, Olino K, Parida L, Nikolaus J, Zhang M, Zhao S, Wang Y, Huang G, Wan M, Li X, Cao J, Yan Q, Chen X, Newman AM, Halaban R. Integrative molecular and clinical profiling of acral melanoma links focal amplification of 22q11.21 to metastasis. Nature Communications 2022, 13: 898. PMID: 35197475, PMCID: PMC8866401, DOI: 10.1038/s41467-022-28566-4.Peer-Reviewed Original ResearchConceptsAcral melanomaMelanoma subtypesClinical profilingCommon melanoma subtypeImmune checkpoint blockadeCheckpoint blockadeInferior survivalMelanoma cell linesKey molecular driversPoor prognosisTherapeutic targetAnchorage-independent growthImmunomodulatory genesNon-white individualsHotspot mutationsMolecular driversCandidate oncogeneMelanomaApoptotic cell deathLZTR1Focal amplificationTumor promoterCell linesMetastasisTumor suppressor