2020
Acquired Resistance to HER2-Targeted Therapies Creates Vulnerability to ATP Synthase Inhibition
Gale M, Li Y, Cao J, Liu ZZ, Holmbeck MA, Zhang M, Lang SM, Wu L, Do Carmo M, Gupta S, Aoshima K, DiGiovanna MP, Stern DF, Rimm DL, Shadel GS, Chen X, Yan Q. Acquired Resistance to HER2-Targeted Therapies Creates Vulnerability to ATP Synthase Inhibition. Cancer Research 2020, 80: 524-535. PMID: 31690671, PMCID: PMC7002225, DOI: 10.1158/0008-5472.can-18-3985.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Combined Chemotherapy ProtocolsApoptosisBreast NeoplasmsCell ProliferationDrug Resistance, NeoplasmEnzyme InhibitorsFemaleHumansMiceMice, Inbred NODMice, SCIDMitochondrial Proton-Translocating ATPasesOligomycinsReceptor, ErbB-2TrastuzumabTumor Cells, CulturedXenograft Model Antitumor AssaysConceptsResistant cellsHER2-Targeted TherapyTrastuzumab-resistant tumorsNew therapeutic strategiesNovel potential targetDrug-free mediumAntibody therapySynthase inhibitionLow doseTherapeutic strategiesTrastuzumabBreast tumorsHER2TherapyAcquired ResistanceTumorsPotential targetMitochondrial respirationCellsSelective dependencyInhibitionMinimal changesNovel vulnerabilitiesATP synthase inhibitionOligomycin A
2018
Patient-derived conditionally reprogrammed cells maintain intra-tumor genetic heterogeneity
Correa BRS, Hu J, Penalva LOF, Schlegel R, Rimm DL, Galante PAF, Agarwal S. Patient-derived conditionally reprogrammed cells maintain intra-tumor genetic heterogeneity. Scientific Reports 2018, 8: 4097. PMID: 29511269, PMCID: PMC5840339, DOI: 10.1038/s41598-018-22427-1.Peer-Reviewed Original ResearchConceptsDrug target identificationNon-small cell lung cancerCancer cell biologyIntra-tumor genetic heterogeneityDrug discovery effortsMutant-allele tumor heterogeneity (MATH) scoreCell biologyWhole-exome sequencingCell heterogeneityNumber variationsPatient-derived cell culturesDiscovery effortsCR cellsCancer cell linesIntra-tumoral heterogeneityGenetic heterogeneityCell linesExome sequencingTarget identificationCell lung cancerLung cancer modelBiologyCell culturesMolecular characteristicsPrimary cultures
2016
Non-malignant respiratory epithelial cells preferentially proliferate from resected non-small cell lung cancer specimens cultured under conditionally reprogrammed conditions
Gao B, Huang C, Kernstine K, Pelekanou V, Kluger Y, Jiang T, Peters-Hall JR, Coquelin M, Girard L, Zhang W, Huffman K, Oliver D, Kinose F, Haura E, Teer JK, Rix U, Le AT, Aisner DL, Varella-Garcia M, Doebele RC, Covington KR, Hampton OA, Doddapaneni HV, Jayaseelan JC, Hu J, Wheeler DA, Shay JW, Rimm DL, Gazdar A, Minna JD. Non-malignant respiratory epithelial cells preferentially proliferate from resected non-small cell lung cancer specimens cultured under conditionally reprogrammed conditions. Oncotarget 2016, 5: 11114-11126. PMID: 28052041, PMCID: PMC5355251, DOI: 10.18632/oncotarget.14366.Peer-Reviewed Original ResearchMeSH KeywordsA549 CellsAdultAgedAged, 80 and overBase SequenceCarcinoma, Non-Small-Cell LungCell Line, TumorCell ProliferationCells, CulturedCoculture TechniquesDNA Copy Number VariationsDNA Mutational AnalysisEpithelial CellsFemaleGene Expression ProfilingGenetic Predisposition to DiseaseHumansLung NeoplasmsMaleMiddle AgedMutationRespiratory MucosaTumor Cells, CulturedConceptsNon-small cell lung cancerRespiratory epithelial cellsNon-malignant lungCell lung cancerCRC culturesLung cancerEpithelial cellsResected non-small cell lung cancerPrimary lung cancerNon-malignant samplesLung epithelial cellsRho-kinase inhibitorNon-malignant cellsPrimary NSCLCPrimary tumorDiploid patternOriginal tumorTumor specimensTumor tissueTumorsKinase inhibitorsCancerCancer cellsMRNA expression profilesSmall subpopulation
2012
Cytoplasmic Estrogen Receptor in Breast Cancer
Welsh AW, Lannin DR, Young GS, Sherman ME, Figueroa JD, Henry NL, Ryden L, Kim C, Love RR, Schiff R, Rimm DL. Cytoplasmic Estrogen Receptor in Breast Cancer. Clinical Cancer Research 2012, 18: 118-126. PMID: 21980134, PMCID: PMC3263348, DOI: 10.1158/1078-0432.ccr-11-1236.Peer-Reviewed Original ResearchConceptsEstrogen receptorCytoplasmic stainingCytoplasmic ERCytoplasmic estrogen receptorSpecific cytoplasmic stainingCell line seriesHuman breast tumorsQuantitative immunofluorescent analysisRoutine clinical valueRetrospective cohortTamoxifen resistanceBreast cancerLower incidencePreclinical modelsClinical valueTissue microarrayPatient controlsBreast tumorsNumber of casesClinical specimensMultiple antibodiesWestern blotAverage incidenceAntibodiesCohort
2011
β-Catenin Signaling Controls Metastasis in Braf-Activated Pten-Deficient Melanomas
Damsky WE, Curley DP, Santhanakrishnan M, Rosenbaum LE, Platt JT, Rothberg BE, Taketo MM, Dankort D, Rimm DL, McMahon M, Bosenberg M. β-Catenin Signaling Controls Metastasis in Braf-Activated Pten-Deficient Melanomas. Cancer Cell 2011, 20: 741-754. PMID: 22172720, PMCID: PMC3241928, DOI: 10.1016/j.ccr.2011.10.030.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, DifferentiationBenzamidesBeta CateninCell Transformation, NeoplasticColorectal NeoplasmsEnzyme ActivationGene Knockdown TechniquesHumansImatinib MesylateKaplan-Meier EstimateLung NeoplasmsLymphatic MetastasisMelanocytesMelanoma, ExperimentalMiceMice, 129 StrainMice, Inbred C57BLMice, TransgenicPhosphorylationPiperazinesProtein StabilityProto-Oncogene Proteins B-rafProto-Oncogene Proteins c-aktPTEN PhosphohydrolasePyrimidinesSignal TransductionSkin NeoplasmsSplenic NeoplasmsTranscription, GeneticTumor Cells, CulturedConceptsΒ-catenin levelsPI3K/AktLymph nodesMetastatic tumorsFrequent metastasisTumor differentiationMalignant melanomaMAPK/ERKMelanoma metastasesMouse modelControl metastasisHuman melanomaMelanomaMetastasisΒ-catenin stabilizationPTEN lossCentral mediatorMetastasis regulatorsΒ-cateninSpecific changesFunctional implicationsWntLung
2009
Growth factor receptor-bound protein-7 (Grb7) as a prognostic marker and therapeutic target in breast cancer
Nadler Y, González AM, Camp RL, Rimm DL, Kluger HM, Kluger Y. Growth factor receptor-bound protein-7 (Grb7) as a prognostic marker and therapeutic target in breast cancer. Annals Of Oncology 2009, 21: 466-473. PMID: 19717535, PMCID: PMC2826097, DOI: 10.1093/annonc/mdp346.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBiomarkers, TumorBlotting, WesternBreast NeoplasmsCarcinoma, Ductal, BreastCarcinoma, LobularFemaleFluorescent Antibody TechniqueFollow-Up StudiesGRB7 Adaptor ProteinHumansImage Processing, Computer-AssistedMiddle AgedPrognosisReceptor, ErbB-2Survival RateTissue Array AnalysisTumor Cells, CulturedYoung AdultConceptsHER2/neuBreast cancerPrognostic markerHER2/neu-positive breast cancerGRB7 expressionHigh HER2/neuNeu-positive breast cancerHER2/neu overexpressionPrimary breast cancerBreast cancer patientsIndependent prognostic markerNode-positive subsetValuable prognostic markerProtein 7Cy5-conjugated antibodiesMultivariable analysisWorse prognosisEntire cohortCancer patientsNeu overexpressionTissue microarrayTherapeutic targetCancerNeuPatientsPhosphatidylinositol-3-Kinase as a Therapeutic Target in Melanoma
Aziz SA, Davies M, Pick E, Zito C, Jilaveanu L, Camp RL, Rimm DL, Kluger Y, Kluger HM. Phosphatidylinositol-3-Kinase as a Therapeutic Target in Melanoma. Clinical Cancer Research 2009, 15: 3029-3036. PMID: 19383818, PMCID: PMC4431617, DOI: 10.1158/1078-0432.ccr-08-2768.Peer-Reviewed Original ResearchMeSH KeywordsBrain NeoplasmsCell ProliferationChromonesEnzyme InhibitorsHumansImmunoblottingImmunoenzyme TechniquesMelanomaMorpholinesNevus, PigmentedPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPhosphorylationProtein Array AnalysisSkin NeoplasmsTissue Array AnalysisTumor Cells, CulturedConceptsPhosphatidylinositol-3 kinasePI3K inhibitorsExpression of p85PI3KP110alpha subunitPathway membersK inhibitorsCell linesPI3K pathway membersReverse phase protein arrayGood drug targetPhase protein arrayPI3K pathwayTargets of drugsCellular processesPhospho-Akt levelsPI3K inhibitionMelanoma cell linesDrug targetsFull activationP85K pathwayLY294002Protein arraysResistant cell lines
2007
Definition of a direct extracellular interaction between Met and E‐cadherin
Reshetnikova G, Troyanovsky S, Rimm DL. Definition of a direct extracellular interaction between Met and E‐cadherin. Cell Biology International 2007, 31: 366-373. PMID: 17336101, DOI: 10.1016/j.cellbi.2007.01.022.Peer-Reviewed Original ResearchConceptsBT-549 cellsE-cadherinCadherin-dependent cell-cell contactsHT-29 cellsE-cadherin interactsHepatocyte growth factorCell-cell adhesionCell-cell contactCross-linking studiesDirect extracellular interactionTyrosine kinase receptor expressionExtracellular interactionsMolecular mechanismsExtracellular domainIntracellular compartmentsPhysical interactionCellular presentationFirst evidenceGrowth factorCellsBT-549HT-29ExpressionReceptor expressionMetS
2006
Direct Interaction of the C-Terminal Domain of α-Catenin and F-Actin is Necessary for Stabilized Cell-Cell Adhesion
Pappas DJ, Rimm DL. Direct Interaction of the C-Terminal Domain of α-Catenin and F-Actin is Necessary for Stabilized Cell-Cell Adhesion. Cell Communication & Adhesion 2006, 13: 151-170. PMID: 16798615, DOI: 10.1080/15419060600726142.Peer-Reviewed Original ResearchConceptsF-actinF-actin interactionCell-cell adhesionC-terminal domainCell-cell contactFilamentous actin cytoskeletonActin cosedimentationActin cytoskeletonAdherens junctionsΑ-cateninColon carcinoma cell lineBasic residuesFusion proteinSingle residueAdhesive phenotypeDrop aggregationC-terminalAdhesive stateCarcinoma cell linesCharge mutationsDirect interactionIndirect binding mechanismsEpithelial monolayersCell linesBinding mechanism
2002
Tissue microarray‐based analysis shows phospho‐β‐catenin expression in malignant melanoma is associated with poor outcome
Kielhorn E, Provost E, Olsen D, D'Aquila TG, Smith BL, Camp RL, Rimm DL. Tissue microarray‐based analysis shows phospho‐β‐catenin expression in malignant melanoma is associated with poor outcome. International Journal Of Cancer 2002, 103: 652-656. PMID: 12494474, DOI: 10.1002/ijc.10893.Peer-Reviewed Original ResearchConceptsMalignant melanomaTissue microarray-based studyTissue microarray-based analysisWorse overall survivalDepth of invasionImmuno-histochemical analysisPhospho-specific antibodiesPhospho-β-catenin expressionOverall survivalMetastatic lesionsPrimary lesionPoor outcomePrognostic markerMelanomaUnique subsetNuclear stainingAntibodiesCatenin antibodyMicroarray-based analysisLesionsOutcomesCatenin expressionSer33/37/Thr41Microarray-based studiesHuman tissuesAlterations of Smad signaling in human breast carcinoma are associated with poor outcome: a tissue microarray study.
Xie W, Mertens JC, Reiss DJ, Rimm DL, Camp RL, Haffty BG, Reiss M. Alterations of Smad signaling in human breast carcinoma are associated with poor outcome: a tissue microarray study. Cancer Research 2002, 62: 497-505. PMID: 11809701.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBreast NeoplasmsCell DivisionCell LineDNA-Binding ProteinsFemaleGenes, BRCA1Genes, BRCA2Germ-Line MutationHeterozygoteHumansImmunohistochemistryKeratinocytesMammary Glands, AnimalMiceMice, Inbred BALB CPhosphorylationPregnancyPrognosisSignal TransductionSmad2 ProteinSmad3 ProteinSmad4 ProteinTrans-ActivatorsTransforming Growth Factor betaTumor Cells, CulturedConceptsHuman breast cancer cell linesBreast cancer cell linesHuman breast carcinomaBreast cancerCancer cell linesBreast carcinomaCell linesStage II breast cancerAxillary lymph node metastasisHuman breast cancer developmentHER2/neu expressionSmad signalingParticular histological subtypeProgesterone receptor expressionLymph node metastasisShorter overall survivalTGF-beta type II receptorTissue microarray studyBreast carcinoma specimensBreast cancer developmentTransgenic mouse modelHuman breast cancerHereditary breast cancerTGF-beta receptor signalingGrowth factor-beta signaling
2001
Truncated DCC Reduces N-Cadherin/Catenin Expression and Calcium-Dependent Cell Adhesion in Neuroblastoma Cells
Reyes-Múgica M, Meyerhardt J, Rzasa J, Rimm D, Johnson K, Wheelock M, Reale M. Truncated DCC Reduces N-Cadherin/Catenin Expression and Calcium-Dependent Cell Adhesion in Neuroblastoma Cells. Laboratory Investigation 2001, 81: 201-210. PMID: 11232642, DOI: 10.1038/labinvest.3780228.Peer-Reviewed Original ResearchMeSH KeywordsAlpha CateninBeta CateninCadherinsCalciumCell AdhesionCell Adhesion MoleculesCell AggregationColorectal NeoplasmsCytoskeletal ProteinsDCC ReceptorDesmogleinsDesmoplakinsGene Expression Regulation, NeoplasticGenes, DCCHumansNeuroblastomaReceptors, Cell SurfaceRecombinant ProteinsSequence DeletionTrans-ActivatorsTransfectionTumor Cells, CulturedTumor Suppressor ProteinsConceptsCalcium-dependent cell adhesionCell adhesionN-cadherinCell-cell contactCalcium-dependent aggregationCell aggregation studiesNorthern blot analysisNeuroblastoma cellsDCC proteinProtein functionNeural developmentFunctional linkColorectal cancer (DCC) proteinCellular migrationHuman neuroblastoma cell lineNeuroblastoma cell linesProteinBlot analysisCancer proteinsProtein levelsCell processesCell linesOverexpressionCatenin expressionDiminished expression
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
1998
Expression of c‐met is a strong independent prognostic factor in breast carcinoma
Ghoussoub R, Dillon D, D'Aquila T, Rimm E, Fearon E, Rimm D. Expression of c‐met is a strong independent prognostic factor in breast carcinoma. Cancer 1998, 82: 1513-1520. PMID: 9554529, DOI: 10.1002/(sici)1097-0142(19980415)82:8<1513::aid-cncr13>3.0.co;2-7.Peer-Reviewed Original ResearchConceptsBreast carcinomaIndependent predictorsStrong independent prognostic factorCox proportional hazards modelGrowth factorIndependent prognostic factorLymph node statusSubset of patientsInvasive ductal carcinomaUseful prognostic markerProportional hazards modelBreast tumor specimensHepatocyte growth factorNegative patientsPrognostic factorsAggressive diseaseDuctal carcinomaNode statusPrognostic valuePrognostic markerTumor specimensHazards modelPatientsPredictive valueSurvival rateA Mutation in α-Catenin Disrupts Adhesion in Clone A Cells Without Perturbing its Actin and β-Catenin Binding Activity
Roe S, Koslov E, Rimm D. A Mutation in α-Catenin Disrupts Adhesion in Clone A Cells Without Perturbing its Actin and β-Catenin Binding Activity. Cell Communication & Adhesion 1998, 5: 283-296. PMID: 9762469, DOI: 10.3109/15419069809040298.Peer-Reviewed Original ResearchMeSH KeywordsActinsAlpha CateninBeta CateninCadherinsCell AdhesionCloning, MolecularColonic NeoplasmsCytoskeletal ProteinsCytoskeletonDesmoplakinsExonsGamma CateninHeLa CellsHumansIntercellular JunctionsMutationOctoxynolPrecipitin TestsProtein BindingRecombinant Fusion ProteinsReverse Transcriptase Polymerase Chain ReactionRNA, MessengerSequence Analysis, DNASolubilityTrans-ActivatorsTransfectionTumor Cells, CulturedConceptsN-terminusE-cadherin-catenin complexBundles F-actinCo-sedimentation assaysCell-cell adhesionFull-length proteinClone A cellsCo-precipitation experimentsInternal deletion mutationsWhole cell lysatesAdhesive complexesMutant proteinsA mutantsMutant bindsHuman colon carcinoma cell lineColon carcinoma cell lineMutant formsLength proteinWild typeCytoplasmic connectionsF-actinAdhesive phenotypeDeletion mutationsCell lysatesCarcinoma cell lines
1997
Vinculin Is Associated with the E-cadherin Adhesion Complex*
Hazan R, Kang L, Roe S, Borgen P, Rimm D. Vinculin Is Associated with the E-cadherin Adhesion Complex*. Journal Of Biological Chemistry 1997, 272: 32448-32453. PMID: 9405455, DOI: 10.1074/jbc.272.51.32448.Peer-Reviewed Original ResearchConceptsE-cadherin complexAdhesion complexesMDA-MB-468 cellsCalcium-dependent cell-cell adhesionE-cadherin adhesion complexAlpha-catenin geneCadherin-dependent adhesionCell-cell adhesionCell adhesion complexesE-cadherinCell linesAlpha-catenin expressionAlpha cateninReciprocal immunoprecipitationCytoplasmic interactionsCoprecipitation analysisAnti-vinculin antibodiesVinculinCadherinCytoplasmic connectionsFusion proteinE-cadherin expressionSame binding siteMDA-MB-468 breast cancer cell lineCell lysatesTranscriptional 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
1996
Expression of a candidate cadherin in T lymphocytes.
Cepek KL, Rimm DL, Brenner MB. Expression of a candidate cadherin in T lymphocytes. Proceedings Of The National Academy Of Sciences Of The United States Of America 1996, 93: 6567-6571. PMID: 8692857, PMCID: PMC39065, DOI: 10.1073/pnas.93.13.6567.Peer-Reviewed Original ResearchConceptsCell adhesion eventsV8 protease digestionHuman T-cell leukemic cell lineT-cell leukemic cell lineCytoplasmic domainHomotypic adhesion moleculeCadherinLeukemic cell linesAdhesion eventsMolecular massProtease digestionHomotypic adhesionHeterotypic adhesionE-cadherinPeptide mapsSpeciesCell linesEpithelial cellsWider roleMucosal epithelial cellsAdhesion moleculesIntestinal intraepithelial T lymphocytesPan-cadherinCellsSolid tissues
1995
Frequent alterations in E-cadherin and alpha- and beta-catenin expression in human breast cancer cell lines.
Pierceall W, Woodard A, Morrow J, Rimm D, Fearon E. Frequent alterations in E-cadherin and alpha- and beta-catenin expression in human breast cancer cell lines. Oncogene 1995, 11: 1319-26. PMID: 7478552.Peer-Reviewed Original ResearchMeSH KeywordsAlpha CateninBase SequenceBeta CateninBlotting, SouthernBlotting, WesternBreast NeoplasmsCadherinsCytoskeletal ProteinsFemaleGene DeletionGene ExpressionHumansMolecular Sequence DataMutationOligodeoxyribonucleotidesPolymerase Chain ReactionPolymorphism, Single-Stranded ConformationalReceptor, ErbB-2RibonucleasesTrans-ActivatorsTumor Cells, CulturedConceptsAlpha-catenin proteinE-cadherin transcriptE-cadherinE-cadherin expressionBeta-catenin expressionCell linesBreast cancer cell linesEpithelial cell-cell interactionsCancer cell linesBeta-catenin proteinCancer-derived cell linesMembrane cytoskeletal proteinsCell-cell interactionsBreast cancer-derived cell linesE-cadherin geneHuman breast cancer-derived cell linesLoss of functionTransmembrane proteinAdherens junctionsCytoskeletal matrixCadherin proteinCytoskeletal proteinsTranscript levelsFrequent alterationsSequence alterations