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
2019
A novel anti-melanoma SRC-family kinase inhibitor
Halaban R, Bacchiocchi A, Straub R, Cao J, Sznol M, Narayan D, Allam A, Krauthammer M, Mansour TS. A novel anti-melanoma SRC-family kinase inhibitor. Oncotarget 2019, 10: 2237-2251. PMID: 31040916, PMCID: PMC6481345, DOI: 10.18632/oncotarget.26787.Peer-Reviewed Original ResearchSrc family kinase inhibitorMAPK inhibitorTranscription factor MITFPatient-derived melanoma cellsPI3K activityKinase inhibitorsSynergistic growth inhibitionGrowth arrestMelanoma cell linesK activityProteolytic degradationCell linesERBB2 inhibitionOncogene expressionMelanoma therapyTumor growthDrug resistanceMelanoma cellsGrowth inhibitionAlternative targetsActivity leadInhibitorsPP2ASHP2Inhibition
2012
Preexisting MEK1 Exon 3 Mutations in V600E/KBRAF Melanomas Do Not Confer Resistance to BRAF Inhibitors
Shi H, Moriceau G, Kong X, Koya RC, Nazarian R, Pupo GM, Bacchiocchi A, Dahlman KB, Chmielowski B, Sosman JA, Halaban R, Kefford RF, Long GV, Ribas A, Lo RS. Preexisting MEK1 Exon 3 Mutations in V600E/KBRAF Melanomas Do Not Confer Resistance to BRAF Inhibitors. Cancer Discovery 2012, 2: 414-424. PMID: 22588879, PMCID: PMC3594852, DOI: 10.1158/2159-8290.cd-12-0022.Peer-Reviewed Original ResearchConceptsBRAF inhibitorsActivating mutationsObjective tumor responseMEK1/2 inhibitorMEK1 mutationsP-ERK1/2 levelsBRAF-mutant melanomaMelanoma cell linesAdvanced melanomaAntitumor responseExon 3 mutationsTumor responseDisease progressionMelanomaBRAFi resistanceDrug sensitivitySignificant alterationsPatientsCell linesInhibitorsBaselineMutationsExon 3Widespread use
2011
MicroRNA signatures differentiate melanoma subtypes
Chan E, Patel R, Nallur S, Ratner E, Bacchiocchi A, Hoyt K, Szpakowski S, Godshalk S, Ariyan S, Sznol M, Halaban R, Krauthammer M, Tuck D, Slack FJ, Weidhaas JB. MicroRNA signatures differentiate melanoma subtypes. Cell Cycle 2011, 10: 1845-1852. PMID: 21543894, PMCID: PMC3233487, DOI: 10.4161/cc.10.11.15777.Peer-Reviewed Original ResearchDetecting copy number status and uncovering subclonal markers in heterogeneous tumor biopsies
Parisi F, Ariyan S, Narayan D, Bacchiocchi A, Hoyt K, Cheng E, Xu F, Li P, Halaban R, Kluger Y. Detecting copy number status and uncovering subclonal markers in heterogeneous tumor biopsies. BMC Genomics 2011, 12: 230. PMID: 21569352, PMCID: PMC3114747, DOI: 10.1186/1471-2164-12-230.Peer-Reviewed Original ResearchConceptsCopy number statusMelanoma samplesSingle nucleotide polymorphism arrayHigh-throughput technologiesNext-generation sequencing dataHigh-throughput techniquesCopy number profilesHigh-throughput assaysNucleotide polymorphism arrayNumber statusCopy number alterationsTranscriptome sequencingNext-generation sequencingRNA-seqSingle exonSNP arraySequencing dataMelanoma cell linesNumerous aberrationsPolymorphism arrayNovel aberrationsNumber alterationsSubclonal heterogeneitySitu hybridizationAllelic imbalance
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
1997
Regulation of fibroblast growth factor 2 expression in melanoma cells by the c-MYB proto-oncoprotein.
Miglarese M, Halaban R, Gibson N. Regulation of fibroblast growth factor 2 expression in melanoma cells by the c-MYB proto-oncoprotein. Molecular Cancer Research 1997, 8: 1199-210. PMID: 9372243.Peer-Reviewed Original ResearchConceptsFGF-2 promoterMurine c-MybSK-MEL-2 human melanoma cellsC-MybFunctional DNA-binding domainHuman melanoma cellsDNA-binding domainMelanoma cellsAutocrine growthPutative MybC-myb mRNATranscription factorsEctopic expressionPromoter regionFibroblast growth factorBasic fibroblast growth factorMelanoma cell linesReporter plasmidNormal melanocytesFibroblast growth factor-2 expressionPromoterGrowth factor 2 expressionMYBFGF-2 proteinCell linesAberrant retention of tyrosinase in the endoplasmic reticulum mediates accelerated degradation of the enzyme and contributes to the dedifferentiated phenotype of amelanotic melanoma cells
Halaban R, Cheng E, Zhang Y, Moellmann G, Hanlon D, Michalak M, Setaluri V, Hebert D. Aberrant retention of tyrosinase in the endoplasmic reticulum mediates accelerated degradation of the enzyme and contributes to the dedifferentiated phenotype of amelanotic melanoma cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 1997, 94: 6210-6215. PMID: 9177196, PMCID: PMC21028, DOI: 10.1073/pnas.94.12.6210.Peer-Reviewed Original ResearchMeSH KeywordsAdultCalcium-Binding ProteinsCalnexinCalreticulinCell DifferentiationCells, CulturedCoculture TechniquesEndoplasmic ReticulumEnzyme PrecursorsHumansInfant, NewbornKineticsMelanocytesMelanomaMolecular ChaperonesMolecular WeightMonophenol MonooxygenasePhenotypeRibonucleoproteinsSkin NeoplasmsTime FactorsTumor Cells, CulturedConceptsEndoplasmic reticulumNormal melanocytesER chaperone calnexinMelanin synthesisMalignant melanocytesMelanoma cellsChaperone bindingAberrant retentionChaperone calnexinGolgi compartmentSubcellular localizationAmelanotic melanoma cell lineKey enzymeMelanoma cell linesMaturation of tyrosinaseAmelanotic melanoma cellsKinetics of synthesisInhibitor sensitivityDedifferentiated phenotypeProteolytic degradationCell linesProteasome inhibitorsEnzymeProteasomeImmature forms
1993
KIT ligand (mast cell growth factor) inhibits the growth of KIT-expressing melanoma cells.
Zakut R, Perlis R, Eliyahu S, Yarden Y, Givol D, Lyman S, Halaban R. KIT ligand (mast cell growth factor) inhibits the growth of KIT-expressing melanoma cells. Oncogene 1993, 8: 2221-9. PMID: 7687762.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceCell DivisionHematopoietic Cell Growth FactorsHumansMelanomaMolecular Sequence DataNeoplasm ProteinsPhosphorylationProtein-Tyrosine KinasesProto-Oncogene MasProto-Oncogene ProteinsProto-Oncogene Proteins c-kitRNA, MessengerRNA, NeoplasmStem Cell FactorTumor Cells, CulturedConceptsMast cell growth factorMelanoma cell linesNormal melanocyte developmentMelanoma cellsAberrant signal transductionMetastatic melanoma cell linesCell linesActivation of KITMelanocyte developmentSignal transductionKIT proto-oncogeneKinase activationKIT mRNAKit ligandNormal melanocytesProto-oncogeneKIT kinaseCell growth factorBiological responsesGrowth factorHuman melanomaMelanocytesCellsKIT expressionNeoplastic melanocytesHuman Melanoma Cells but Not Normal Melanocytes Express Vascular Endothelial Growth Factor Receptors
Gitaygoren H, Halaban R, Neufeld G. Human Melanoma Cells but Not Normal Melanocytes Express Vascular Endothelial Growth Factor Receptors. Biochemical And Biophysical Research Communications 1993, 190: 702-709. PMID: 8439321, DOI: 10.1006/bbrc.1993.1106.Peer-Reviewed Original ResearchMeSH KeywordsCells, CulturedCross-Linking ReagentsEndothelial Growth FactorsHeparinHumansIn Vitro TechniquesLymphokinesMelanocytesMelanomaProtein-Tyrosine KinasesReceptors, MitogenReceptors, Vascular Endothelial Growth FactorRecombinant ProteinsVascular Endothelial Growth Factor AVascular Endothelial Growth FactorsConceptsVascular endothelial growth factorHuman melanoma cellsMelanoma cellsMalignant transformationVEGF receptorsVascular endothelial growth factor receptorEndothelial growth factor receptorNormal melanocytesEndothelial growth factorGrowth factor receptorMelanoma cell linesHeparin-like moleculesAngiogenic factorsEndothelial cellsSpecific mitogenAberrant expressionGrowth factorFactor receptorLigand/receptor interactionsReceptorsMalignant melanocytesRadioactive ligandExogenous heparinPossible involvementReceptor interaction
1989
Isolation, Chromosomal Mapping, and Expression of the Mouse Tyrosinase Gene
Kwon B, Haq A, Wakulchik M, Kestler D, Barton D, Francke U, Lamoreux M, Whitney J, Halaban R. Isolation, Chromosomal Mapping, and Expression of the Mouse Tyrosinase Gene. Journal Of Investigative Dermatology 1989, 93: 589-594. PMID: 2507645, DOI: 10.1111/1523-1747.ep12319693.Peer-Reviewed Original ResearchConceptsMouse tyrosinaseTyrosinase geneMouse chromosome 7Mouse tyrosinase geneSomatic cell hybridsSouthern blot analysisChromosomal mappingGenomic clonesCell hybridsPromoter sequencesTATA elementAlbino locusChromosome 7Melanoma cell linesCDNA probeNormal melanocytesTyrosinase mRNABackcross miceBlot analysisFarthest upstreamCell linesDeletion miceGenesLociCloudman S
1985
Primary Melanoma Cells of the Vertical Growth Phase: Similarities to Metastatic Cells2
Herlyn M, Balaban G, Bennicelli J, Guerry D, Halaban R, Herlyn D, Elder D, Maul G, Steplewski Z, Nowell P, Clark W, Koprowski H. Primary Melanoma Cells of the Vertical Growth Phase: Similarities to Metastatic Cells2. Journal Of The National Cancer Institute 1985, 74: 283-289. PMID: 3856042, DOI: 10.1093/jnci/74.2.283.Peer-Reviewed Original ResearchConceptsVertical growth phaseMetastatic melanoma cellsMelanoma cellsMetastatic lesionsPrimary melanomaMetastatic cellsMelanoma-associated antigensMixed hemadsorption assaysPrimary melanoma cellsLong-term cultured cellsMetastatic melanoma cell linesGrowth phaseMelanoma cell linesRadial growth phaseMalignant melanomaNude micePopulation-doubling timeNonrandom abnormalitiesFlow cytometryHemadsorption assaysMonoclonal antibodiesMelanomaPatientsCell linesLesions