2024
Vascular mimicry as a facilitator of melanoma brain metastasis
Provance O, Oria V, Tran T, Caulfield J, Zito C, Aguirre-Ducler A, Schalper K, Kluger H, Jilaveanu L. Vascular mimicry as a facilitator of melanoma brain metastasis. Cellular And Molecular Life Sciences 2024, 81: 188. PMID: 38635031, PMCID: PMC11026261, DOI: 10.1007/s00018-024-05217-z.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainBrain NeoplasmsCell LineHumansMelanomaMiceNeovascularization, PathologicTranscription FactorsConceptsVascular mimicryBrain metastasesMouse model of metastatic melanomaIncreased risk of metastasisAssociated with tumor volumeMelanoma brain metastasesRisk of metastasisSurvival of miceFuture treatment regimensCell line modelsTumor suppressor pathwayMetastatic melanomaTumor volumeSolid tumorsTreatment regimensTumor typesPoor prognosisHippo tumor suppressor pathwayIncreased riskMouse modelDownstream targets YAPMelanomaMetastasisSuppressor pathwayTumor
2022
Coupled fibromodulin and SOX2 signaling as a critical regulator of metastatic outgrowth in melanoma
Oria VO, Zhang H, Zito CR, Rane CK, Ma XY, Provance OK, Tran TT, Adeniran A, Kluger Y, Sznol M, Bosenberg MW, Kluger HM, Jilaveanu LB. Coupled fibromodulin and SOX2 signaling as a critical regulator of metastatic outgrowth in melanoma. Cellular And Molecular Life Sciences 2022, 79: 377. PMID: 35737114, PMCID: PMC9226089, DOI: 10.1007/s00018-022-04364-5.Peer-Reviewed Original ResearchMeSH KeywordsBrain NeoplasmsFibromodulinHumansMelanomaNeoplasm MetastasisSignal TransductionSOXB1 Transcription FactorsTranscription FactorsConceptsTumor suppressor Hippo pathwayNovel regulatory mechanismTumor vasculogenic mimicryMetastatic outgrowthExtracellular matrix componentsHippo pathwayRegulatory mechanismsMolecular eventsTumor-stroma interactionsCritical regulatorMetastatic competenceProgenitor markersProliferative stateFunctional roleFunctional studiesSOX2Vasculogenic mimicryDistinct phenotypesMatrix componentsEarly developmentFmodHigh expressionCritical processOutgrowthImportant role
2020
Regulation of eIF2α by RNF4 Promotes Melanoma Tumorigenesis and Therapy Resistance
Avitan-Hersh E, Feng Y, Oknin Vaisman A, Abu Ahmad Y, Zohar Y, Zhang T, Lee JS, Lazar I, Sheikh Khalil S, Feiler Y, Kluger H, Kahana C, Brown K, Ruppin E, Ronai ZA, Orian A. Regulation of eIF2α by RNF4 Promotes Melanoma Tumorigenesis and Therapy Resistance. Journal Of Investigative Dermatology 2020, 140: 2466-2477. PMID: 32360601, PMCID: PMC8081033, DOI: 10.1016/j.jid.2020.04.008.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarcinogenesisCell Line, TumorDrug Resistance, NeoplasmEukaryotic Initiation Factor-2FemaleGene Expression Regulation, NeoplasticHumansKaplan-Meier EstimateMelanomaMiceMitogen-Activated Protein KinasesNuclear ProteinsOncogenesPrognosisProtein Kinase InhibitorsProtein StabilityProto-Oncogene Proteins B-rafSkinSkin NeoplasmsTranscription FactorsUbiquitinationXenograft Model Antitumor AssaysConceptsUbiquitin ligase RNF4Elongation factor alphaPatient-derived melanomasIntegrated stress responseTherapy resistancePositive feed-forward loopTranscription factor 4Feed-forward loopOncogenic translationMolecular machineryMajor clinical challengePhosphorylated eIF2αHallmark of melanomaXenograft mouse modelHomologous proteinsStress responseMAPK inhibitorProtein stabilizationMelanoma tumorigenesisTumorigenic propertiesPoor prognosisFactor alphaClinical challengeMouse modelRNF4
2016
Genomic characterization of sarcomatoid transformation in clear cell renal cell carcinoma
Bi M, Zhao S, Said JW, Merino MJ, Adeniran AJ, Xie Z, Nawaf CB, Choi J, Belldegrun AS, Pantuck AJ, Kluger HM, Bilgüvar K, Lifton RP, Shuch B. Genomic characterization of sarcomatoid transformation in clear cell renal cell carcinoma. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: 2170-2175. PMID: 26864202, PMCID: PMC4776463, DOI: 10.1073/pnas.1525735113.Peer-Reviewed Original ResearchMeSH KeywordsAgedCarcinoma, Renal CellCell DedifferentiationDNA Mismatch RepairDNA-Binding ProteinsExomeFemaleGenes, p53HumansKidney NeoplasmsLoss of HeterozygosityMaleMiddle AgedMutationNuclear ProteinsOncogenesPolymorphism, Single NucleotidePrognosisTranscription FactorsTumor Suppressor ProteinsUbiquitin ThiolesteraseConceptsClear cell renal cell carcinomaCell renal cell carcinomaRenal cell carcinomaSarcomatoid elementsCarcinomatous elementsCell carcinomaSomatic single nucleotide variantsVon Hippel-Lindau tumor suppressorPoor-prognosis cancerTreatment of patientsTumor protein p53 (TP53) mutationsMismatch repair deficiencyRich interaction domain 1ASarcomatoid featuresPoor prognosisUnknown pathogenesisPolybromo-1TP53 mutationsP53 mutationsSarcomatoid transformationPan-cancer genesExome sequencingTumorsRepair deficiencyProtein 1
2008
Expression 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
2006
Characterizing disease states from topological properties of transcriptional regulatory networks
Tuck DP, Kluger HM, Kluger Y. Characterizing disease states from topological properties of transcriptional regulatory networks. BMC Bioinformatics 2006, 7: 236. PMID: 16670008, PMCID: PMC1482723, DOI: 10.1186/1471-2105-7-236.Peer-Reviewed Original ResearchConceptsTranscriptional regulatory networksRegulatory networksTranscription factorsTranscriptional networksRegulated genesGene deregulationExpression profilesDiseased statesGene regulatory networksCentrality of genesGene expression experimentsGene expression profilesGene expression studiesGene centralityRegulatory linkExpression experimentsExpression studiesGene linksGenesCell typesExpression datasetsGene subsetsDifferential activityNormal cellsRemarkable degreeAssociation between pathways in regulatory networks
Kluger Y, Kluger H, Tuck D. Association between pathways in regulatory networks. Annual International Conference Of The IEEE Engineering In Medicine And Biology Society (EMBC) 2006, 2006: 2036-2040. PMID: 17946929, DOI: 10.1109/iembs.2006.260730.Peer-Reviewed Original ResearchMeSH KeywordsComputer SimulationGene Expression RegulationModels, BiologicalProteomeSignal TransductionStatistics as TopicTranscription FactorsTranscriptional ActivationConceptsRegulatory networksCo-regulated pathwaysHuman regulatory networkRegulatory network connectivityDistinct cell typesTranscriptional regulatory levelCondition-specific networksGene regulationIndividual genesCell statesTranscriptional activityCell typesCell progressionExpression signaturesNumerous pathwaysGene profilesRemarkable connectivityMultiple pathwaysPathwayGenesRegulatory levelsRegulationExpressionCellsNotable differences
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