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 inhibitors
2022
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 tumorsMetastasis
2009
GOLPH3 modulates mTOR signalling and rapamycin sensitivity in cancer
Scott KL, Kabbarah O, Liang MC, Ivanova E, Anagnostou V, Wu J, Dhakal S, Wu M, Chen S, Feinberg T, Huang J, Saci A, Widlund HR, Fisher DE, Xiao Y, Rimm DL, Protopopov A, Wong KK, Chin L. GOLPH3 modulates mTOR signalling and rapamycin sensitivity in cancer. Nature 2009, 459: 1085-1090. PMID: 19553991, PMCID: PMC2753613, DOI: 10.1038/nature08109.Peer-Reviewed Original ResearchConceptsTarget of rapamycinTrans-Golgi networkHuman cancersGenome-wide copy number analysisCopy number analysisRetromer complexGolgi proteinsHuman cancer cellsRapamycin sensitivityNew oncogeneGOLPH3Integrative analysisPotent oncogeneGenomic profilesBiochemical dataCancer cellsFunction studiesNumber analysisYeastSolid tumor typesCell sizeOncogeneMTORRapamycinMTOR inhibitorsAnalysis of Drosophila Segmentation Network Identifies a JNK Pathway Factor Overexpressed in Kidney Cancer
Liu J, Ghanim M, Xue L, Brown CD, Iossifov I, Angeletti C, Hua S, Nègre N, Ludwig M, Stricker T, Al-Ahmadie HA, Tretiakova M, Camp RL, Perera-Alberto M, Rimm DL, Xu T, Rzhetsky A, White KP. Analysis of Drosophila Segmentation Network Identifies a JNK Pathway Factor Overexpressed in Kidney Cancer. Science 2009, 323: 1218-1222. PMID: 19164706, PMCID: PMC2756524, DOI: 10.1126/science.1157669.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsApoptosisCarcinoma, Renal CellCell LineCompound Eye, ArthropodDrosophila melanogasterDrosophila ProteinsEmbryo, NonmammalianFushi Tarazu Transcription FactorsGene Expression ProfilingGene Regulatory NetworksHomeodomain ProteinsHumansJanus KinasesKidneyKidney NeoplasmsMolecular Sequence DataNervous SystemNuclear ProteinsPhosphoprotein PhosphatasesPhosphorylationRepressor ProteinsSignal TransductionTranscription FactorsTranscription, GeneticConceptsTranscription factorsClear cell renal cell carcinomaCell renal cell carcinomaKey transcription factorDrosophila segmentation networkConserved roleEmbryonic segmentationDrosophila melanogasterUbiquitin E3JNK signalingDependent apoptosisSPOPRenal cell carcinomaSPOP expressionKidney cancerTumor necrosis factorNew roleDrosophilaMelanogasterPuckeredGenesSignalingOverexpressedIdentificationApoptosis
2008
Thyroid Transcription Factor 1 Is an Independent Prognostic Factor for Patients With Stage I Lung Adenocarcinoma
Anagnostou VK, Syrigos KN, Bepler G, Homer RJ, Rimm DL. Thyroid Transcription Factor 1 Is an Independent Prognostic Factor for Patients With Stage I Lung Adenocarcinoma. Journal Of Clinical Oncology 2008, 27: 271-278. PMID: 19064983, DOI: 10.1200/jco.2008.17.0043.Peer-Reviewed Original ResearchConceptsThyroid transcription factor-1Stage I lung adenocarcinomaTTF1 expressionTranscription factor 1Lung adenocarcinomaStage IIndependent lower riskMedian overall survivalProtein expressionIndependent prognostic factorPotential prognostic parametersSubgroup of patientsFactor 1Overall survivalPrognostic factorsPatient survivalPrognostic parametersPrognostic stratificationLung cancerFavorable outcomeSitu protein expressionIndependent cohortLower riskPatientsAdenocarcinomaEstrogen receptor co-activator (AIB1) protein expression by automated quantitative analysis (AQUA) in a breast cancer tissue microarray and association with patient outcome
Harigopal M, Heymann J, Ghosh S, Anagnostou V, Camp RL, Rimm DL. Estrogen receptor co-activator (AIB1) protein expression by automated quantitative analysis (AQUA) in a breast cancer tissue microarray and association with patient outcome. Breast Cancer Research And Treatment 2008, 115: 77-85. PMID: 18521745, DOI: 10.1007/s10549-008-0063-9.Peer-Reviewed Original ResearchMeSH KeywordsAlgorithmsAutomationBiomarkers, TumorBreast NeoplasmsFemaleGene Expression Regulation, NeoplasticHumansMultivariate AnalysisNuclear Receptor Coactivator 3Oligonucleotide Array Sequence AnalysisPrognosisProportional Hazards ModelsReceptors, EstrogenReceptors, ProgesteroneRegression AnalysisTranscription FactorsTreatment OutcomeConceptsHigh AIB1 expressionTranscription intermediary factor 2Poor patient outcomesAIB1 expressionTissue microarrayPatient outcomesHER2/neu statusBreast cancer tissue microarrayFluorescent immunohistochemical stainingWorse overall survivalUnivariate survival analysisBreast cancer specimensCancer tissue microarrayHER2/neuCoregulatory proteinsCox univariate survival analysesBreast tissue microarraysOverall survivalER statusPR statusPrognostic significanceIndependent associationBreast cancerPrognostic biomarkerImmunohistochemical stainingExpression patterns and prognostic value of Bag-1 and Bcl-2 in breast cancer
Nadler Y, Camp RL, Giltnane JM, Moeder C, Rimm DL, Kluger HM, Kluger Y. Expression patterns and prognostic value of Bag-1 and Bcl-2 in breast cancer. Breast Cancer Research 2008, 10: r35. PMID: 18430249, PMCID: PMC2397537, DOI: 10.1186/bcr1998.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic AgentsBiomarkers, TumorBreast NeoplasmsDNA-Binding ProteinsDrug Resistance, NeoplasmFemaleFluorescent Antibody TechniqueFollow-Up StudiesGene Expression Regulation, NeoplasticHumansImmunohistochemistryKaplan-Meier EstimateLymphatic MetastasisMiddle AgedPredictive Value of TestsPrognosisProportional Hazards ModelsProtein Array AnalysisProto-Oncogene Proteins c-bcl-2Receptors, EstrogenReceptors, ProgesteroneTranscription FactorsTreatment OutcomeConceptsNode-positive subsetHER2/neuProgesterone receptorBreast cancerEstrogen receptorBcl-2 expressionBAG-1 expressionImproved survivalBcl-2Anti-apoptotic mediator Bcl-2Breast tumorsSteroid receptor positivitySubset of patientsBAG-1Antihormonal therapyFavorable prognosisReceptor positivityMultivariable analysisPathological variablesEntire cohortPrognostic valuePrognostic markerImproved outcomesLarge cohortClinical development
2005
Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma
Garraway LA, Widlund HR, Rubin MA, Getz G, Berger AJ, Ramaswamy S, Beroukhim R, Milner DA, Granter SR, Du J, Lee C, Wagner SN, Li C, Golub TR, Rimm DL, Meyerson ML, Fisher DE, Sellers WR. Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma. Nature 2005, 436: 117-122. PMID: 16001072, DOI: 10.1038/nature03664.Peer-Reviewed Original ResearchMeSH KeywordsCell Line, TumorCell LineageCell SurvivalChromosomes, Human, Pair 3Disease ProgressionDNA-Binding ProteinsGene AmplificationGene DosageGene Expression Regulation, NeoplasticGenomicsHumansIn Situ Hybridization, FluorescenceMelanomaMicrophthalmia-Associated Transcription FactorOncogenesPolymerase Chain ReactionPolymorphism, Single NucleotideTranscription FactorsConceptsMITF gene expressionDNA amplification eventsIntegrative genomic analysisLineage-survival oncogenePossible drug targetsGenomics effortsGenomic analysisGenetic dataGene expressionMelanoma formationAmplification eventsMelanoma genesDrug targetsCancer cell linesGenetic alterationsCell linesMITFMelanoma cellsHuman melanomaMalignant melanomaGenesMelanomaOncogeneExpressionCells
2004
Expression Profiling Reveals Novel Pathways in the Transformation of Melanocytes to Melanomas
Hoek K, Rimm DL, Williams KR, Zhao H, Ariyan S, Lin A, Kluger HM, Berger AJ, Cheng E, Trombetta ES, Wu T, Niinobe M, Yoshikawa K, Hannigan GE, Halaban R. Expression Profiling Reveals Novel Pathways in the Transformation of Melanocytes to Melanomas. Cancer Research 2004, 64: 5270-5282. PMID: 15289333, DOI: 10.1158/0008-5472.can-04-0731.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkers, TumorCell Transformation, NeoplasticCohort StudiesDown-RegulationGene Expression ProfilingGene Expression Regulation, NeoplasticHumansLymphatic MetastasisMelanocytesMelanomaMiceNuclear ProteinsOligonucleotide Array Sequence AnalysisPrognosisSignal TransductionSkin NeoplasmsSurvival RateTranscription FactorsTransfectionTwist-Related Protein 1Ubiquitin ThiolesteraseConceptsGlobal differential gene expressionMembrane trafficking eventsNovel pathwayNormal melanocytesHelix protein TwistAdditional transcriptional regulatorsDifferential gene expressionMelanoma cellsTransformation of melanocytesCpG promoter methylationNormal human melanocytesTrafficking eventsTranscriptional regulatorsEmbryonic developmentGrowth suppressorChromosomal regionsExpression profilingGene expressionNotch pathwayOligonucleotide microarraysMelanoma tissue microarrayDifferential expressionGenesHuman melanocytesGrowth advantage
2003
Subcellular localization of activating transcription factor 2 in melanoma specimens predicts patient survival.
Berger AJ, Kluger HM, Li N, Kielhorn E, Halaban R, Ronai Z, Rimm DL. Subcellular localization of activating transcription factor 2 in melanoma specimens predicts patient survival. Cancer Research 2003, 63: 8103-7. PMID: 14678960.Peer-Reviewed Original ResearchConceptsATF2 expressionTranscription factor 2Melanoma specimensUseful prognostic markerEarly-stage melanomaWeak cytoplasmic stainingStrong nuclear stainingFactor 2Mean followCutaneous specimensLocalized diseaseOverall survivalIndependent predictorsPreclinical findingsClark levelClinicopathological dataPatient survivalPoor outcomePrognostic valueWorse outcomesPrognostic markerPoor survivalPreclinical modelsClinical significanceImmunohistochemical staining
2001
Parathyroid hormone-related protein maintains mammary epithelial fate and triggers nipple skin differentiation during embryonic breast development
Foley J, Dann P, Hong J, Cosgrove J, Dreyer B, Rimm D, Dunbar M, Philbrick W, Wysolmerski J. Parathyroid hormone-related protein maintains mammary epithelial fate and triggers nipple skin differentiation during embryonic breast development. Development 2001, 128: 513-525. PMID: 11171335, DOI: 10.1242/dev.128.4.513.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBeta CateninCell DifferentiationCell LineageCytoskeletal ProteinsDNA-Binding ProteinsEpidermal CellsEpidermisEpithelial CellsFemaleGene Expression Regulation, DevelopmentalHistocytochemistryLymphoid Enhancer-Binding Factor 1Mammary Glands, AnimalMiceMice, KnockoutMice, TransgenicModels, BiologicalNipplesParathyroid Hormone-Related ProteinProteinsReceptor, Parathyroid Hormone, Type 1Receptors, Parathyroid HormoneSignal TransductionTrans-ActivatorsTranscription FactorsTransgenesConceptsPTH/PTHrP receptorCell fateHormone-related proteinMammary epithelial cell fateMammary mesenchymeCell fate decisionsEpithelial cell fatePTHrP receptorEmbryonic mammary glandMesenchymal cellsType I PTH/PTHrP receptorEmbryonic mammary developmentMammary epithelial cellsParathyroid hormone-related proteinEpithelial cellsEpithelial fateEpidermal fateFate decisionsEpithelial morphogenesisAbsence of PTHrPMesenchymal expressionVentral epidermisProper developmentSkin differentiationCombination of loss
1999
Beta- and gamma-catenin mutations, but not E-cadherin inactivation, underlie T-cell factor/lymphoid enhancer factor transcriptional deregulation in gastric and pancreatic cancer.
Caca K, Kolligs FT, Ji X, Hayes M, Qian J, Yahanda A, Rimm DL, Costa J, Fearon ER. Beta- and gamma-catenin mutations, but not E-cadherin inactivation, underlie T-cell factor/lymphoid enhancer factor transcriptional deregulation in gastric and pancreatic cancer. Molecular Cancer Research 1999, 10: 369-76. PMID: 10392898.Peer-Reviewed Original ResearchMeSH KeywordsAdenomatous Polyposis Coli ProteinAmino Acid SequenceAnimalsBeta CateninCadherinsCytoskeletal ProteinsDesmoplakinsDNA-Binding ProteinsGamma CateninGene Expression Regulation, NeoplasticHMGB ProteinsHumansLymphoid Enhancer-Binding Factor 1Molecular Sequence DataMutagenesisPancreatic NeoplasmsStomach NeoplasmsTCF Transcription FactorsTrans-ActivatorsTranscription Factor 7-Like 1 ProteinTranscription FactorsTranscription, GeneticTumor Cells, CulturedConceptsPhosphorylation sitesMutant proteinsGlycogen synthase kinase 3beta phosphorylation sitesGlycogen synthase kinase-3betaFactor transcription factorsPotential phosphorylation sitesSynthase kinase-3betaTCF transcriptional activityE-cadherin inactivationNH2-terminal deletionsRole of APCImportant binding partnerSerine 28TCF transcriptionTranscriptional deregulationT-cell factorBinding partnerTranscription factorsAPC proteinKinase-3betaTranscriptional activityNH2 terminusAdenomatous polyposis coli (APC) mutationsCell adhesionPancreatic cancer lines
1997
Transcriptional defects underlie loss of E-cadherin expression in breast cancer.
Ji X, Woodard AS, Rimm DL, Fearon ER. Transcriptional defects underlie loss of E-cadherin expression in breast cancer. Molecular Cancer Research 1997, 8: 773-8. PMID: 9218871.Peer-Reviewed Original ResearchMeSH KeywordsAntimetabolites, AntineoplasticAzacitidineBreast NeoplasmsCadherinsCloning, MolecularDecitabineDNA MethylationDNA-Binding ProteinsGene Expression Regulation, NeoplasticHumansPromoter Regions, GeneticTrans-ActivatorsTranscription Factor AP-2Transcription FactorsTranscription, GeneticTumor Cells, CulturedConceptsE-cad expressionBreast cancerEpithelial cancersHuman breast cancer cell linesMost breast cancersDifferent epithelial cancersBreast cancer cell linesMajority of cancersE-cadherin expressionCancer cell linesCell adhesion moleculeProgression eventsCancerAdhesion moleculesTumor heterogeneityE-cadherinFunctional assaysCell linesSomatic mutationsE-cad geneGene expression differencesExpressionPromoter activityGene expressionReporter gene constructs