2016
RASopathy Gene Mutations in Melanoma
Halaban R, Krauthammer M. RASopathy Gene Mutations in Melanoma. Journal Of Investigative Dermatology 2016, 136: 1755-1759. PMID: 27236105, PMCID: PMC4992636, DOI: 10.1016/j.jid.2016.05.095.Peer-Reviewed Original ResearchConceptsRASopathy mutationsRAS/mitogen-activated protein kinaseRAS/mitogen-activated protein kinase (MAPK) pathwayMitogen-activated protein kinase pathwayMitogen-activated protein kinaseProtein kinase pathwayAmino acid substitutionsNext-generation sequencingProtein kinasePathway genesKinase pathwaySequencing dataDriver genesAcid substitutionsGenomic abnormalitiesMutationsLegius syndromeGenesAbundant mutationsGermline mutationsGene mutationsPathwaySignificant overlapKinaseMelanomagenesisAMPK promotes tolerance to Ras pathway inhibition by activating autophagy
Sanduja S, Feng Y, Mathis RA, Sokol ES, Reinhardt F, Halaban R, Gupta PB. AMPK promotes tolerance to Ras pathway inhibition by activating autophagy. Oncogene 2016, 35: 5295-5303. PMID: 27041569, PMCID: PMC6086350, DOI: 10.1038/onc.2016.70.Peer-Reviewed Original ResearchConceptsCellular energy sensor AMPEnergy sensor AMPPathway inhibitorTargeted inhibitorsRas-Raf pathwayDrug-tolerant cellsPathway inhibitionOncogenic RasProtein kinaseRaf signalingRas pathway inhibitionReduced growthAMPKAutophagyPathway mutationsCancer cellsResistant cellsKey mechanismPathwayInhibitorsCellsToleranceKinaseSignalingInhibition
2015
Combination Therapy with Anti–CTLA-4 and Anti–PD-1 Leads to Distinct Immunologic Changes In Vivo
Das R, Verma R, Sznol M, Boddupalli CS, Gettinger SN, Kluger H, Callahan M, Wolchok JD, Halaban R, Dhodapkar MV, Dhodapkar KM. Combination Therapy with Anti–CTLA-4 and Anti–PD-1 Leads to Distinct Immunologic Changes In Vivo. The Journal Of Immunology 2015, 194: 950-959. PMID: 25539810, PMCID: PMC4380504, DOI: 10.4049/jimmunol.1401686.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntigens, SurfaceAntineoplastic Combined Chemotherapy ProtocolsCTLA-4 AntigenCytokinesGene Expression ProfilingGene Expression Regulation, NeoplasticHumansImmunophenotypingIpilimumabLymphocytes, Tumor-InfiltratingNeoplasmsNivolumabProgrammed Cell Death 1 ReceptorSignal TransductionT-Lymphocyte SubsetsConceptsPD-1T cellsCTLA-4Checkpoint blockadeCombination therapyReceptor occupancyCombination immune checkpoint blockadeCTLA-4 immune checkpointsPD-1 receptor occupancyTransitional memory T cellsAnti-PD-1 therapyAnti CTLA-4Immune-based combinationsPD-1 blockadeSoluble IL-2RImmune checkpoint blockadeNK cell functionMemory T cellsTherapy-induced changesT cell activationTumor T cellsHuman T cellsRemarkable antitumor effectImmunologic changesImmunologic effects
2013
RAC1P29S is a spontaneously activating cancer-associated GTPase
Davis MJ, Ha BH, Holman EC, Halaban R, Schlessinger J, Boggon TJ. RAC1P29S is a spontaneously activating cancer-associated GTPase. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 912-917. PMID: 23284172, PMCID: PMC3549122, DOI: 10.1073/pnas.1220895110.Peer-Reviewed Original ResearchAmino Acid SubstitutionAnimalsCell Surface ExtensionsChlorocebus aethiopsCOS CellsCrystallography, X-RayEnzyme ActivationGenetic Association StudiesGuanosine TriphosphateHumansHydrolysisKineticsMelanomaMiceMicroscopy, FluorescenceModels, MolecularMutation, MissenseNIH 3T3 CellsOncogenesRac1 GTP-Binding ProteinRecombinant Fusion ProteinsSignal TransductionStatic Electricity
2012
Type II p21-activated kinases (PAKs) are regulated by an autoinhibitory pseudosubstrate
Ha BH, Davis MJ, Chen C, Lou HJ, Gao J, Zhang R, Krauthammer M, Halaban R, Schlessinger J, Turk BE, Boggon TJ. Type II p21-activated kinases (PAKs) are regulated by an autoinhibitory pseudosubstrate. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 16107-16112. PMID: 22988085, PMCID: PMC3479536, DOI: 10.1073/pnas.1214447109.Peer-Reviewed Original ResearchConceptsP21-activated kinasePhosphorylated activation loopActivation loop phosphorylationCritical proline residueRho family GTPasesBcl-2/BclCellular morphological changesPAK regulationStructure-guided approachLoop phosphorylationPseudosubstrate regionAutoinhibitory pseudosubstratePseudosubstrate motifActivation loopCatalytic domainSrc SH3Cell motilityMolecular basisProline residuesKey effectorsCell deathPAK4SH3KinasePseudosubstrate
2011
Phosphoproteomic Screen Identifies Potential Therapeutic Targets in Melanoma
Tworkoski K, Singhal G, Szpakowski S, Zito CI, Bacchiocchi A, Muthusamy V, Bosenberg M, Krauthammer M, Halaban R, Stern DF. Phosphoproteomic Screen Identifies Potential Therapeutic Targets in Melanoma. Molecular Cancer Research 2011, 9: 801-812. PMID: 21521745, PMCID: PMC3117976, DOI: 10.1158/1541-7786.mcr-10-0512.Peer-Reviewed Original ResearchMeSH KeywordsApoptosisCell Line, TumorCell MovementCell ProliferationErbB ReceptorsGene Expression Regulation, NeoplasticGene Knockdown TechniquesHEK293 CellsHumansInfant, NewbornMelanocytesMelanomaPhosphoproteinsPhosphorylationProteomicsReceptor Protein-Tyrosine KinasesReceptor, IGF Type 2RNA, Small InterferingSignal TransductionSkin NeoplasmsSTAT3 Transcription FactorConceptsTherapeutic targetReceptor tyrosine kinasesMelanoma cellsPotential therapeutic targetIdentifies potential therapeutic targetsActive receptor tyrosine kinasesTyrosine kinaseMelanoma cell migrationReceptor expressionBreast cancerAxl knockdownAutocrine circuitTherapeutic interventionsCancer subtypesReceptor tyrosine kinase activationTyrosine kinase activationNovel targetActivated receptorsAxlRNA knockdownMelanomaCell migrationHER3KnockdownIGF1RFuture perspectives in melanoma research. Meeting report from the "Melanoma Research: a bridge Naples-USA. Naples, December 6th-7th2010"
Ascierto PA, De Maio E, Bertuzzi S, Palmieri G, Halaban R, Hendrix M, Kashani-sabet M, Ferrone S, Wang E, Cochran A, Rivoltini L, Lee PP, Fox BA, Kirkwood JM, Ullmann CD, Lehmann FF, Sznol M, Schwartzentruber DJ, Maio M, Flaherty K, Galon J, Ribas A, Yang J, Stroncek DF, Mozzillo N, Marincola FM. Future perspectives in melanoma research. Meeting report from the "Melanoma Research: a bridge Naples-USA. Naples, December 6th-7th2010". Journal Of Translational Medicine 2011, 9: 32. PMID: 21439082, PMCID: PMC3078100, DOI: 10.1186/1479-5876-9-32.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkers, TumorClinical Trials as TopicHumansItalyMelanomaMiceResearchSignal TransductionUnited States
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
2000
The Regulation of Normal Melanocyte Proliferation
Halaban R. The Regulation of Normal Melanocyte Proliferation. Pigment Cell & Melanoma Research 2000, 13: 4-14. PMID: 10761990, DOI: 10.1034/j.1600-0749.2000.130103.x.Peer-Reviewed Original ResearchConceptsTranscription factorsIntracellular signal transduction cascadesE2F transcription factorsImmediate early response genesSignal transduction cascadeHepatocyte growth factor/scatter factorGrowth factorGrowth factor/scatter factorE2F transcriptional activityCyclin-dependent kinasesSynergistic growth factorsNormal human melanocytesPocket proteinsRetinoblastoma familyPeptide growth factorsStem cell factorTransduction cascadeNormal melanocyte proliferationEctopic expressionResponse genesTranscriptional activityFibroblast growth factorMolecular eventsHuman melanocytesIntermediate effectors
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
1997
Diminished TCR signaling in cutaneous T cell lymphoma is associated with decreased activities of Zap70, Syk and membrane-associated Csk
Fargnoli M, Edelson R, Berger C, Chimenti S, Couture C, Mustelin T, Halaban R. Diminished TCR signaling in cutaneous T cell lymphoma is associated with decreased activities of Zap70, Syk and membrane-associated Csk. Leukemia 1997, 11: 1338-1346. PMID: 9264390, DOI: 10.1038/sj.leu.2400745.Peer-Reviewed Original ResearchMeSH KeywordsAdultCSK Tyrosine-Protein KinaseEnzyme ActivationEnzyme PrecursorsHumansImmunophenotypingIntracellular Signaling Peptides and ProteinsLymphoma, T-Cell, CutaneousPhosphotyrosineProtein-Tyrosine KinasesReceptors, Antigen, T-CellSignal TransductionSkin NeoplasmsSrc-Family KinasesSyk KinaseT-LymphocytesZAP-70 Protein-Tyrosine KinaseConceptsCutaneous T-cell lymphomaProtein tyrosine kinasesFunction of membersSignal transduction moleculesWeak mitogenic responseActivity of SykTCR ζ-chainCell surface receptorsTCR/CD3Membrane-bound fractionCellular proteinsTyrosyl phosphorylationT-cell lymphomaTyrosine phosphorylationTransduction moleculesLck kinaseTyrosine kinaseDistinct familiesΖ chainEffector moleculesKinaseSurface receptorsEnzymatic activityCell lymphomaNeoplastic cells
1996
Growth factors and melanomas.
Halaban R. Growth factors and melanomas. Seminars In Oncology 1996, 23: 673-81. PMID: 8970586.Peer-Reviewed Original ResearchMeSH KeywordsCarrier ProteinsCell Cycle ProteinsCell Transformation, NeoplasticCyclin-Dependent Kinase Inhibitor p16Cyclin-Dependent KinasesEndothelinsFibroblast Growth Factor 2Gene Expression Regulation, NeoplasticGrowth SubstancesHumansMelanocytesMelanomaReceptors, Growth FactorSignal TransductionConceptsCyclin-dependent kinasesFibroblast growth factorNormal human melanocytesMast/stem cell growth factorCell cycleCDK inhibitor p16INK4Human melanocytesMelanoma cellsGrowth factorHepatocyte growth factor/scatter factorStem cell growth factorGrowth factor/scatter factorSynergistic growth factorsNeuropeptide endothelin-1Cell cycle progressionPhosphorylation of retinoblastomaGrowth constraintsWild-type p53Unregulated expressionTranscriptional activityNegative regulatorCycle progressionResult of inactivationBasic fibroblast growth factorInhibitory complex
1994
Signal Transduction in Normal and Malignant Melanocytes
HALABAN R. Signal Transduction in Normal and Malignant Melanocytes. Pigment Cell & Melanoma Research 1994, 7: 89-95. PMID: 8066025, DOI: 10.1111/j.1600-0749.1994.tb00026.x.Peer-Reviewed Original Research
1993
Pigmentation and Proliferation of Human Melanocytes and the Effects of Melanocyte‐Stimulating Hormone and Ultraviolet B Lighta
HALABAN R, TYRRELL L, LONGLEY J, YARDEN Y, RUBIN J. Pigmentation and Proliferation of Human Melanocytes and the Effects of Melanocyte‐Stimulating Hormone and Ultraviolet B Lighta. Annals Of The New York Academy Of Sciences 1993, 680: 290-301. PMID: 7685575, DOI: 10.1111/j.1749-6632.1993.tb19691.x.Peer-Reviewed Original ResearchGrowth Regulation in Normal and Malignant Melanocytes
Halaban R. Growth Regulation in Normal and Malignant Melanocytes. Recent Results In Cancer Research 1993, 128: 133-150. PMID: 8356315, DOI: 10.1007/978-3-642-84881-0_10.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DivisionCell Transformation, NeoplasticGrowth SubstancesHumansMelanocytesMelanomaReference ValuesSignal TransductionSkin NeoplasmsConceptsNormal human melanocytesHuman melanocytesSignal transduction pathwaysGrowth factorMalignant melanocytesGrowth factors/receptorsTransduction pathwaysGrowth regulationConstitutive activationBiochemical basisBiochemical eventsNormal melanocytesGrowth phaseRadial growth phaseMalignant stateMelanocytesMelanoma cellsNormal counterpartsPreneoplastic cellsReceptor activityInappropriate productionCellsMetastatic melanoma lesionsActivationReceptors
1992
Met and hepatocyte growth factor/scatter factor signal transduction in normal melanocytes and melanoma cells.
Halaban R, Rubin J, Funasaka Y, Cobb M, Boulton T, Faletto D, Rosen E, Chan A, Yoko K, White W. Met and hepatocyte growth factor/scatter factor signal transduction in normal melanocytes and melanoma cells. Oncogene 1992, 7: 2195-206. PMID: 1331934.Peer-Reviewed Original ResearchConceptsHGF/SFMast cell growth factorSignal transductionBasic fibroblast growth factorProtein kinase/extracellular signal-regulated kinaseHuman melanocytesMalignant human melanocytesExtracellular signal-regulated kinaseHepatocyte growth factor/scatter factorGrowth factor/scatter factorSignal-regulated kinaseActivation of microtubuleProto-oncogene c-metTransmembrane tyrosine kinase receptorActivation of METC-MetTyrosine kinase receptorsNormal human melanocytesGrowth factorMouse melanocytesTyrosine phosphorylationBiological roleFibroblast growth factorKinase receptorsConstitutive activity
1991
Proliferation and malignant transformation of melanocytes.
Halaban R, Moellmann G. Proliferation and malignant transformation of melanocytes. Critical Reviews™ In Oncogenesis 1991, 2: 247-58. PMID: 1958709.Peer-Reviewed Original ResearchConceptsActive receptor tyrosine kinasesTissue-specific genesReceptor tyrosine kinasesSignal transmission pathwaysGrowth factor receptorLow molecular weight inhibitorsUnregulated expressionCertain chromosomesTyrosine kinaseGenesNormal melanocytesMalignant transformationMouse fibroblastsFactor receptorDrug designWeight inhibitorsKaryotypic changesKinaseMelanoma-prone familiesGrowth factorOncogeneHuman melanomaMelanocytesMelanoma growthTransmission pathways