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
2005
Melanocyte and Keratinocyte Carcinogenesis: p53 Family Protein Activities and Intersecting mRNA Expression Profiles
Kulesz-Martin M, Lagowski J, Fei S, Pelz C, Sears R, Powell MB, Halaban R, Johnson J. Melanocyte and Keratinocyte Carcinogenesis: p53 Family Protein Activities and Intersecting mRNA Expression Profiles. Journal Of Investigative Dermatology Symposium Proceedings 2005, 10: 142-152. PMID: 16363065, DOI: 10.1111/j.1087-0024.2005.200405.x.Peer-Reviewed Original ResearchRb/E2F: A two-edged sword in the melanocytic system
Halaban R. Rb/E2F: A two-edged sword in the melanocytic system. Cancer And Metastasis Reviews 2005, 24: 339-356. PMID: 15986142, DOI: 10.1007/s10555-005-1582-z.Peer-Reviewed Original ResearchConceptsE2F transcriptional activityTranscriptional activityActivated cell surface receptorsRb/E2F pathwayRb-E2F interactionCyclin-dependent kinase activityCell cycle genesE2F complex formationMelanoma cellsCdk inhibitors p16INK4ACell cycle progressionDependent kinase activityExpression of E2FCell surface receptorsGene repressionCycle genesE2F pathwayCDK activityApoptosis genesKinase activityB-RafCycle progressionRb interactionPhosphorylated RbTumor suppressor
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 stainingThe tyrphostin AG1024 accelerates the degradation of phosphorylated forms of retinoblastoma protein (pRb) and restores pRb tumor suppressive function in melanoma cells.
von Willebrand M, Zacksenhaus E, Cheng E, Glazer P, Halaban R. The tyrphostin AG1024 accelerates the degradation of phosphorylated forms of retinoblastoma protein (pRb) and restores pRb tumor suppressive function in melanoma cells. Cancer Research 2003, 63: 1420-9. PMID: 12649208.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Cycle ProteinsCell DivisionCyclin-Dependent KinasesDNA-Binding ProteinsE2F Transcription FactorsE2F1 Transcription FactorE2F3 Transcription FactorHumansMAP Kinase Signaling SystemMelanocytesMelanomaMiceMitogen-Activated Protein Kinase 1PhosphorylationRetinoblastoma ProteinTranscription FactorsTyrphostinsUbiquitinConceptsTumor suppressive functionPhosphorylated formCell surface receptor kinaseMitogen-activated protein kinase/extracellular signal-regulated kinase pathwayProtein kinase/extracellular signal-regulated kinase pathwayExtracellular signal-regulated kinase (ERK) pathwaySignal-regulated kinase pathwayMelanoma cellsPhosphorylation/inactivationCyclin-dependent kinase 2Insulin-like growth factor 1 receptorActivation of pRbReceptor kinase activitySpecific chemical inhibitorsGrowth factor 1 receptorFactor 1 receptorPocket proteinsRetinoblastoma familyMelanoma cell proliferationReceptor kinaseProtein degradationKinase pathwayRetinoblastoma proteinKinase activityMelanoma cell growth
2000
Deregulated E2f Transcriptional Activity in Autonomously Growing Melanoma Cells
Halaban R, Cheng E, Smicun Y, Germino J. Deregulated E2f Transcriptional Activity in Autonomously Growing Melanoma Cells. Journal Of Experimental Medicine 2000, 191: 1005-1016. PMID: 10727462, PMCID: PMC2193116, DOI: 10.1084/jem.191.6.1005.Peer-Reviewed Original ResearchMeSH KeywordsCarrier ProteinsCell Cycle ProteinsCell DivisionCells, CulturedCellular SenescenceCulture Media, ConditionedCyclin-Dependent KinasesCyclinsDNA-Binding ProteinsDown-RegulationDrosophila ProteinsE2F Transcription FactorsE2F1 Transcription FactorE2F2 Transcription FactorE2F3 Transcription FactorE2F4 Transcription FactorE2F5 Transcription FactorE2F6 Transcription FactorEnzyme InhibitorsFlavonoidsHumansMelanocytesMelanomaPhosphorylationPiperidinesProtein BindingRetinoblastoma-Binding Protein 1Trans-ActivatorsTranscription Factor DP1Transcription FactorsTumor Cells, CulturedConceptsExternal growth factorsE2F DNAPocket proteinsCyclin-dependent kinase 4Normal melanocytesTranscriptional activityRetinoblastoma tumor suppressor proteinMelanoma cellsMalignant human melanocytesE2F transcription factorsE2F family membersE2F transcriptional activityTumor suppressor proteinGel shift analysisCell cycle progressionForm of pRBGrowth factorContinuous high expressionE2F activityOnly family memberTranscription factorsProtein DNASuppressor proteinFamily membersMolecular basis
1999
Melanoma Cell Autonomous Growth: The Rb/E2F Pathway
Halaban R. Melanoma Cell Autonomous Growth: The Rb/E2F Pathway. Cancer And Metastasis Reviews 1999, 18: 333-343. PMID: 10721488, DOI: 10.1023/a:1006396104073.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarrier ProteinsCell CycleCell Cycle ProteinsCell DivisionCyclin-Dependent KinasesDNA-Binding ProteinsE2F Transcription FactorsHumansMelanocytesMelanomaPhosphorylationRetinoblastoma ProteinRetinoblastoma-Binding Protein 1Signal TransductionTranscription Factor DP1Transcription FactorsConceptsPocket proteinsExternal growth factorsNormal melanocytesE2F activityTarget genesRb/E2F pathwayE2F transcription factorsCell surface receptor stimulationMelanoma cellsCell-autonomous growthTumor suppressor proteinClass of enzymesCyclin-dependent kinasesInactivation of pRbConstitutive high expressionGrowth factorCell cycle progressionSurface receptor stimulationMetastatic melanoma cellsRetinoblastoma familySuppressive complexE2F pathwayPositive regulatorTranscription factorsMouse melanocytes
1998
Release of cell cycle constraints in mouse melanocytes by overexpressed mutant E2F1E132, but not by deletion of p16INK4A or p21WAF1/CIP1
Halaban R, Cheng E, Zhang Y, Mandigo C, Miglarese M. Release of cell cycle constraints in mouse melanocytes by overexpressed mutant E2F1E132, but not by deletion of p16INK4A or p21WAF1/CIP1. Oncogene 1998, 16: 2489-2501. PMID: 9627115, DOI: 10.1038/sj.onc.1201773.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarrier ProteinsCell CycleCell Cycle ProteinsCell SurvivalCyclin-Dependent Kinase Inhibitor p16Cyclin-Dependent Kinase Inhibitor p21CyclinsDNA-Binding ProteinsE2F Transcription FactorsE2F1 Transcription FactorGene Expression RegulationHumansMelanocytesMiceMice, NudeMutagenesisProtein BiosynthesisRecombinant Fusion ProteinsRetinoblastoma ProteinRetinoblastoma-Binding Protein 1Tetradecanoylphorbol AcetateTranscription Factor DP1Transcription FactorsConceptsP21WAF1/CIP1Cell cycle progressionMouse melanocytesTarget genesCycle progressionRetinoblastoma tumor suppressor proteinE2F-mediated transactivationCell cycle constraintsTumor suppressor proteinRole of E2F1Deletion of p16INK4AFree E2FExpression of RbGene disruptionSuppressor proteinEctopic expressionHallmark of melanomaTetradecanoyl phorbol 13Loss of p16INK4aConstitutive expressionMelanoma cell linesCell deathNormal melanocytesIndependent growthMelanocyte growth
1996
Growth Regulatory Proteins that Repress Differentiation Markers in Melanocytes Also Downregulate the Transcription Factor Microphthalmia
Halaban R, Böhm M, Dotto P, Moellmann G, Cheng E, Zhang Y. Growth Regulatory Proteins that Repress Differentiation Markers in Melanocytes Also Downregulate the Transcription Factor Microphthalmia. Journal Of Investigative Dermatology 1996, 106: 1266-1272. PMID: 8752668, DOI: 10.1111/1523-1747.ep12348972.Peer-Reviewed Original ResearchConceptsTranscription factorsFibroblast growth factorBasic fibroblast growth factorMelanocyte-specific genesMelanogenic gene expressionTranscription factor microphthalmiaDownregulated transcription factorsDNA consensus siteTyrosinase-related protein 1Human metastatic melanoma cellsImmortalized mouse melanocytesPink-eyed dilutionCloudman S91 mouse melanomaMetastatic melanoma cellsSequestration of p300Transcriptional adaptorGrowth factorE1A mutantsConsensus sitesMouse melanocytesRegulatory proteinsMolecular basisOncogene RasGene expressionTumorigenic transformation
1995
Identification of p90RSK as the probable CREB-Ser133 kinase in human melanocytes.
Böhm M, Moellmann G, Cheng E, Alvarez-Franco M, Wagner S, Sassone-Corsi P, Halaban R. Identification of p90RSK as the probable CREB-Ser133 kinase in human melanocytes. Molecular Cancer Research 1995, 6: 291-302. PMID: 7540859.Peer-Reviewed Original ResearchMeSH KeywordsCell CountCell DivisionCells, CulturedCyclic AMPCyclic AMP Response Element-Binding ProteinDrug SynergismEndothelinsFibroblast Growth Factor 2Growth SubstancesHematopoietic Cell Growth FactorsHepatocyte Growth FactorHumansInfant, NewbornMelanocytesPhosphorylationProtein Serine-Threonine KinasesRecombinant Fusion ProteinsRibosomal Protein S6 KinasesSerineStem Cell FactorTime FactorsTranscription FactorsConceptsSynergistic growth factorsMast/stem cell growth factorHuman melanocytesGrowth factorHepatocyte growth factor/scatter factorActivation of p90RSKGrowth factor/scatter factorStem cell growth factorCAMP-responsive element binding proteinKID domainElement-binding proteinNormal human melanocytesTranscription factor 1Peptide growth factorsSer133 phosphorylationTranscriptional activationCell divisionPhosphorylated stateTranscription factorsInduces phosphorylationRegulatory proteinsSignal transducerFibroblast growth factorBasic fibroblast growth factorBinding protein