Featured Publications
Truncating PREX2 mutations activate its GEF activity and alter gene expression regulation in NRAS-mutant melanoma
Lissanu Deribe Y, Shi Y, Rai K, Nezi L, Amin S, Wu C, Akdemir K, Mahdavi M, Peng Q, Chang Q, Hornigold K, Arold S, Welch H, Garraway L, Chin L. Truncating PREX2 mutations activate its GEF activity and alter gene expression regulation in NRAS-mutant melanoma. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: e1296-e1305. PMID: 26884185, PMCID: PMC4780599, DOI: 10.1073/pnas.1513801113.Peer-Reviewed Original ResearchConceptsPREX2 mutationsCross-species gene expression analysisGuanine nucleotide exchange factor activityNucleotide exchange factor activityGene expression regulationPI3K/PTEN/Akt pathwayExchange factor activityMelanoma developmentPTEN/AKT pathwayCell cycle regulatorsGene expression analysisExpression regulationGEF activityCytoskeleton organizationCDKN1C geneRegulatory regionsExpression analysisGene expressionCycle regulatorsDNA hypomethylationCell cycleChromosome 11Tumor suppressorBiological pathwaysMechanistic basis
2020
Enhancer Reprogramming Confers Dependence on Glycolysis and IGF Signaling in KMT2D Mutant Melanoma
Maitituoheti M, Keung E, Tang M, Yan L, Alam H, Han G, Singh A, Raman A, Terranova C, Sarkar S, Orouji E, Amin S, Sharma S, Williams M, Samant N, Dhamdhere M, Zheng N, Shah T, Shah A, Axelrad J, Anvar N, Lin Y, Jiang S, Chang E, Ingram D, Wang W, Lazar A, Lee M, Muller F, Wang L, Ying H, Rai K. Enhancer Reprogramming Confers Dependence on Glycolysis and IGF Signaling in KMT2D Mutant Melanoma. Cell Reports 2020, 33: 108293. PMID: 33086062, PMCID: PMC7649750, DOI: 10.1016/j.celrep.2020.108293.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarrier ProteinsCell Line, TumorDNA-Binding ProteinsFemaleGenes, Tumor SuppressorGlucoseGlycolysisHistone MethyltransferasesHistone-Lysine N-MethyltransferaseHumansInsulinIntercellular Signaling Peptides and ProteinsMaleMelanomaMiceMice, Inbred C57BLMice, NudeMyeloid-Lymphoid Leukemia ProteinNeoplasm ProteinsReceptor, IGF Type 1Regulatory Sequences, Nucleic AcidSignal TransductionXenograft Model Antitumor AssaysConceptsKMT2D-deficient cellsInsulin growth factorEnhancer reprogrammingIGF1R-AktMelanocyte-specific deletionMutant melanomaMouse modelTumor typesTherapeutic interventionsPharmacological inhibitionPathway inhibitorPotent tumor suppressorIGF signalingGrowth factorMelanomaPooled RNAi screensSomatic point mutationsTumor suppressorKey metabolic pathwaysFrequent lossGlycolysisGlycolysis enzymesTumorigenesisGlycolysis pathwayMetabolic pathwaysKMT2D Deficiency Impairs Super-Enhancers to Confer a Glycolytic Vulnerability in Lung Cancer
Alam H, Tang M, Maitituoheti M, Dhar S, Kumar M, Han C, Ambati C, Amin S, Gu B, Chen T, Lin Y, Chen J, Muller F, Putluri N, Flores E, DeMayo F, Baseler L, Rai K, Lee M. KMT2D Deficiency Impairs Super-Enhancers to Confer a Glycolytic Vulnerability in Lung Cancer. Cancer Cell 2020, 37: 599-617.e7. PMID: 32243837, PMCID: PMC7178078, DOI: 10.1016/j.ccell.2020.03.005.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinoma of LungAnimalsAntimetabolitesApoptosisBiomarkers, TumorCell ProliferationDeoxyglucoseDNA-Binding ProteinsEnhancer Elements, GeneticGene Expression Regulation, NeoplasticGlycolysisHistone-Lysine N-MethyltransferaseHistonesHumansLung NeoplasmsMiceMice, KnockoutMice, NudeMutationMyeloid-Lymphoid Leukemia ProteinNeoplasm ProteinsPeriod Circadian ProteinsPrognosisTumor Cells, CulturedXenograft Model Antitumor AssaysConceptsLung cancerLung-specific lossHuman lung cancer cellsExpression of Per2Lung cancer cellsHistone methyltransferase KMT2DLung tumor suppressorTumor suppressive roleMultiple glycolytic genesLung tumorigenesisEpigenetic modifiersPharmacological inhibitionTherapeutic vulnerabilitiesGlycolytic inhibitorCancerCancer cellsKMT2DFunction mutationsTumor suppressorPer2GlycolysisGlycolytic genesMutationsMice
2012
Investigational agent MLN9708/2238 targets tumor-suppressor miR33b in MM cells
Tian Z, Zhao J, Tai Y, Amin S, Hu Y, Berger A, Richardson P, Chauhan D, Anderson K. Investigational agent MLN9708/2238 targets tumor-suppressor miR33b in MM cells. Blood 2012, 120: 3958-3967. PMID: 22983447, PMCID: PMC3496955, DOI: 10.1182/blood-2012-01-401794.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsBoron CompoundsCell DeathCell Line, TumorCell MovementCell SurvivalCluster AnalysisDrug Resistance, NeoplasmGene Expression ProfilingGene Expression Regulation, NeoplasticGenes, Tumor SuppressorGlycineHumansImidazolesMiceMicroRNAsMultiple MyelomaProto-Oncogene Proteins c-pim-1PyridazinesSignal TransductionXenograft Model Antitumor AssaysConceptsMultiple myelomaMM cellsPim-1Tumor suppressor geneTranscriptional regulationPim-1 overexpressionBiochemical inhibitorsApoptotic signalingRole of miRTumor suppressorMiR33bMM cell viabilityCell deathPatient MM cellsMM xenograft modelNovel therapeutic strategiesLuciferase activityColony formationOverexpressionMiR profilingTumor pathogenesisInvestigational agentsCritical roleRegulationCell viability