2019
Aging-like Spontaneous Epigenetic Silencing Facilitates Wnt Activation, Stemness, and Braf V600E-Induced Tumorigenesis
Tao Y, Kang B, Petkovich DA, Bhandari YR, In J, Stein-O'Brien G, Kong X, Xie W, Zachos N, Maegawa S, Vaidya H, Brown S, Yen R, Shao X, Thakor J, Lu Z, Cai Y, Zhang Y, Mallona I, Peinado MA, Zahnow CA, Ahuja N, Fertig E, Issa JP, Baylin SB, Easwaran H. Aging-like Spontaneous Epigenetic Silencing Facilitates Wnt Activation, Stemness, and Braf V600E-Induced Tumorigenesis. Cancer Cell 2019, 35: 315-328.e6. PMID: 30753828, PMCID: PMC6636642, DOI: 10.1016/j.ccell.2019.01.005.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAge FactorsAgingAnimalsCell Transformation, NeoplasticColonic NeoplasmsDNA MethylationGene Expression Regulation, NeoplasticGene SilencingGenetic Predisposition to DiseaseHumansMice, Inbred NODMice, Mutant StrainsMice, SCIDMutationPhenotypeProto-Oncogene Proteins B-rafStem CellsTime FactorsTissue Culture TechniquesWnt Signaling PathwayConceptsCell fate changesPromoter DNA hypermethylationStem-like stateAging-like phenotypesCpG island methylationFate changesDifferentiation defectsEpigenetic abnormalitiesDNA hypermethylationSimultaneous inactivationWnt pathwayWnt activationPromoter hypermethylationTumorigenesisGenesHypermethylationMethylator phenotypeColon tumorigenesisPhenotypeOrganoidsPrecursor roleCRISPRMethylationSupStemness
2018
DNA Methylation Patterns Separate Senescence from Transformation Potential and Indicate Cancer Risk
Xie W, Kagiampakis I, Pan L, Zhang YW, Murphy L, Tao Y, Kong X, Kang B, Xia L, Carvalho FLF, Sen S, Yen R, Zahnow CA, Ahuja N, Baylin SB, Easwaran H. DNA Methylation Patterns Separate Senescence from Transformation Potential and Indicate Cancer Risk. Cancer Cell 2018, 33: 309-321.e5. PMID: 29438699, PMCID: PMC5813821, DOI: 10.1016/j.ccell.2018.01.008.Peer-Reviewed Original ResearchConceptsDevelopmental genesDNA methylation patternsPromoter hypermethylation eventsEpigenetic patternsMethylation gainMethylation patternsMethylation changesHypermethylation eventsEpigenetic changesTissue agingSenescenceMetabolic regulatorTissue typesGenesTransformation potentialCellsHypermethylationRegulatorCancer risk
2017
Hypomethylating agents synergize with irinotecan to improve response to chemotherapy in colorectal cancer cells
Sharma A, Vatapalli R, Abdelfatah E, McMahon K, Kerner Z, Guzzetta A, Singh J, Zahnow C, Baylin S, Yerram S, Hu Y, Azad N, Ahuja N. Hypomethylating agents synergize with irinotecan to improve response to chemotherapy in colorectal cancer cells. PLOS ONE 2017, 12: e0176139. PMID: 28445481, PMCID: PMC5405959, DOI: 10.1371/journal.pone.0176139.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsATP-Binding Cassette TransportersAzacitidineCaco-2 CellsCamptothecinCell AdhesionCell Line, TumorCell ProliferationColorectal NeoplasmsDNA MethylationDNA RepairGene ExpressionGene Expression ProfilingHCT116 CellsHumansIrinotecanLong Interspersed Nucleotide ElementsMiceMice, Inbred NODMice, SCIDConceptsCRC cell linesColorectal cancerMultiple CRC cell linesPhase 1/2 clinical trialCell linesMetastatic colorectal cancerMajority of patientsNOD-SCID miceColorectal cancer cellsSoft agar assayInitial therapyMetastatic settingCytotoxic chemotherapyCRC treatmentClinical efficacyCancer deathTumor regressionClinical trialsDNA demethylating agentVivo xenograftsChemotherapeutic agentsCancer cellsHCT116 cell linesAgar assayChemotherapy