2015
Downregulation of the Ubiquitin Ligase RNF125 Underlies Resistance of Melanoma Cells to BRAF Inhibitors via JAK1 Deregulation
Kim H, Frederick DT, Levesque MP, Cooper ZA, Feng Y, Krepler C, Brill L, Samuels Y, Hayward NK, Perlina A, Piris A, Zhang T, Halaban R, Herlyn MM, Brown KM, Wargo JA, Dummer R, Flaherty KT, Ronai Z. Downregulation of the Ubiquitin Ligase RNF125 Underlies Resistance of Melanoma Cells to BRAF Inhibitors via JAK1 Deregulation. Cell Reports 2015, 11: 1458-1473. PMID: 26027934, PMCID: PMC4681438, DOI: 10.1016/j.celrep.2015.04.049.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorChromatography, LiquidDown-RegulationDrug Resistance, NeoplasmEnzyme InhibitorsFemaleHeterograftsHumansImmunoblottingImmunohistochemistryImmunoprecipitationJanus Kinase 1Mass SpectrometryMelanomaMiceMice, NudeProto-Oncogene Proteins B-rafRNA, Small InterferingTransfectionUbiquitin-Protein LigasesConceptsBRAF inhibitorsRTK expressionReceptor tyrosine kinasesRemarkable clinical responsesBRAFi-resistant melanomasInhibition of JAK1BRAFi-resistant tumorsClinical responseCombination therapyMost tumorsBRAF mutationsTumor specimensVivo xenograftsBRAFi resistanceMelanoma cellsElevated expressionMelanomaEGFRAdaptive resistanceTumorsRNF125MITF expressionTyrosine kinaseJAK1Downregulation
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 migrationHER3KnockdownIGF1R
1992
Growth Factors, Receptor Kinases, and Protein Tyro sine Phosphatases in Normal and Malignant Melanocytes
Halaban R, Fan B, Ahn J, Funasaka Y, Gitay-Goren H, Neufeld G. Growth Factors, Receptor Kinases, and Protein Tyro sine Phosphatases in Normal and Malignant Melanocytes. Journal Of Immunotherapy 1992, 12: 154-161. PMID: 1445804, DOI: 10.1097/00002371-199210000-00002.Peer-Reviewed Original ResearchConceptsMast cell growth factorReceptor tyrosine kinasesFibroblast growth factorTyrosine kinaseTyrosyl-phosphorylated proteinsExpression of pigmentationTransmembrane receptor tyrosine kinaseHepatocyte growth factorGrowth factorGrowth factor/receptor systemsHuman melanocyte proliferationBasic FGFMelanoma cellsProtein tyrosineReceptor kinasePigment cellsBasic fibroblast growth factorFGF receptorsKinaseHuman melanoma cellsNormal melanocytesKIT kinaseMalignant phenotypeMelanocyte proliferationCell growth factor
1991
Growth factors and tyrosine protein kinases in normal and malignant melanocytes
Halaban R. Growth factors and tyrosine protein kinases in normal and malignant melanocytes. Cancer And Metastasis Reviews 1991, 10: 129-140. PMID: 1873853, DOI: 10.1007/bf00049410.Peer-Reviewed Original ResearchConceptsMast cell growth factorTyrosine kinase activityKinase activityBasic fibroblast growth factorNormal melanocyte proliferationTyrosine kinaseExogenous peptide growth factorsHepatocyte growth factorGrowth factorTyrosine protein kinaseAberrant gene expressionMelanocyte proliferationTransmembrane tyrosine kinaseReceptor tyrosine kinasesEnvironmental growth factorsNormal human melanocytesPeptide growth factorsMouse melanocytesProtein kinaseGrowth factor receptorUncontrolled growthC-kitGene expressionConstitutive expressionFibroblast growth factorProliferation 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