2021
Reprogramming of bivalent chromatin states in NRAS mutant melanoma suggests PRC2 inhibition as a therapeutic strategy
Terranova C, Tang M, Maitituoheti M, Raman A, Ghosh A, Schulz J, Amin S, Orouji E, Tomczak K, Sarkar S, Oba J, Creasy C, Wu C, Khan S, Lazcano R, Wani K, Singh A, Barrodia P, Zhao D, Chen K, Haydu L, Wang W, Lazar A, Woodman S, Bernatchez C, Rai K. Reprogramming of bivalent chromatin states in NRAS mutant melanoma suggests PRC2 inhibition as a therapeutic strategy. Cell Reports 2021, 36: 109410. PMID: 34289358, PMCID: PMC8369408, DOI: 10.1016/j.celrep.2021.109410.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorCell ProliferationChromatinEnhancer of Zeste Homolog 2 ProteinFemaleGTP PhosphohydrolasesHistonesHumansMelanocytesMelanomaMembrane ProteinsMesodermMice, NudeMitogen-Activated Protein Kinase KinasesMutationNeoplasm MetastasisPolycomb Repressive Complex 2Transcription, GeneticTumor BurdenConceptsHistone H3 lysine 27 trimethylationH3 lysine 27 trimethylationBivalent chromatin stateCell identity genesLysine 27 trimethylationKey epigenetic alterationsNRAS mutantsMaster transcription factorBivalent domainsChromatin statePRC2 inhibitionEpigenetic elementsTranscription factorsEpigenetic alterationsGenetic driversMesenchymal phenotypeNRAS-mutant melanomaState profilingTherapeutic vulnerabilitiesInvasive capacityPharmacological inhibitionMutantsTherapeutic strategiesMelanoma samplesMutant melanoma patients
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
2018
An in vivo screen identifies PYGO2 as a driver for metastatic prostate cancer
Lu X, Pan X, Wu C, Zhao D, Feng S, Zang Y, Lee R, Khadka S, Amin S, Jin E, Shang X, Deng P, Luo Y, Morgenlander W, Weinrich J, Lu X, Jiang S, Chang Q, Navone N, Troncoso P, DePinho R, Wang Y. An in vivo screen identifies PYGO2 as a driver for metastatic prostate cancer. Cancer Research 2018, 78: canres.3564.2017. PMID: 29769196, PMCID: PMC6381393, DOI: 10.1158/0008-5472.can-17-3564.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkers, TumorCarcinogenesisCell Line, TumorDisease ProgressionGene Expression Regulation, NeoplasticHEK293 CellsHumansIntracellular Signaling Peptides and ProteinsLymph NodesMaleMiceMice, NudeNeoplasm GradingOncogenesPC-3 CellsProstatic NeoplasmsTranscriptional ActivationUp-RegulationWnt Signaling PathwayConceptsProstate cancer progressionDepth functional analysisCancer progressionWnt/β-catenin signalingCancer cell invasionΒ-catenin signalingFunctional genomicsProstate cancerTranscriptional activationCopy number aberrationsTranscriptomic datasetsFinger 2New oncogenePygo2's functionFunctional driversFunctional analysisLymph nodesImpairs tumor progressionChromosomal instabilityPutative oncogeneCell invasionNumber aberrationsPositive hitsAmplification/overexpressionOncogene