Mesenchymal and MAPK Expression Signatures Associate with Telomerase Promoter Mutations in Multiple Cancers
Stern J, Hibshman G, Hu K, Ferrara S, Costello J, Kim W, Tamayo P, Cech T, Huang F. Mesenchymal and MAPK Expression Signatures Associate with Telomerase Promoter Mutations in Multiple Cancers. Molecular Cancer Research 2020, 18: 1050-1062. PMID: 32276990, PMCID: PMC8020009, DOI: 10.1158/1541-7786.mcr-19-1244.Peer-Reviewed Original ResearchMeSH KeywordsCell Line, TumorChromatin ImmunoprecipitationEpithelial-Mesenchymal TransitionExtracellular Signal-Regulated MAP KinasesGene Expression ProfilingGene Expression Regulation, NeoplasticGene Regulatory NetworksHumansMutationNeoplasmsPromoter Regions, GeneticSequence Analysis, RNASmall Molecule LibrariesTelomeraseTumor MicroenvironmentConceptsCell linesAnalysis of cell linesAdherens junction protein E-cadherinKnock-down experimentsExpression signaturesRAS pathway inhibitorsInhibition of MEK1Promoter mutationsSensitivity to specific drugsCatalytic subunit of telomeraseJunction protein E-cadherinProtein E-cadherinSubunit of telomeraseInvestigational treatment approachesMesenchymal transcription factorsPan-cancer analysisCatalytic subunitEpithelial-to-mesenchymal transitionTranscription factorsCell line growthMutantsPathway effectorsTERT mRNA expressionMAPK signalingProliferative immortalityGαs (GNAS) suppression of the p53 genomic‐stability checkpoint unleashes RAS‐driven oncogenesis
Steffen D, Tiriac H, Valera J, Amornphimoltham P, Kim W, Taylor S, Hunter T, Tamayo P, Gutkind J. Gαs (GNAS) suppression of the p53 genomic‐stability checkpoint unleashes RAS‐driven oncogenesis. The FASEB Journal 2020, 34: 1-1. DOI: 10.1096/fasebj.2020.34.s1.04604.Peer-Reviewed Original ResearchTrp53 tumor suppressor geneCooperation of rasMDM2-mediated p53 ubiquitinationHuman intestinal organoid modelP53 E3 ubiquitin ligaseSquamous cell carcinomaIn vitro ubiquitination assayP53 protein accumulationChemical carcinogen DMBASkin of adult miceTumor suppressor genePhosphorylation of Mdm2Control genome stabilityE3 ubiquitin ligaseRAS mutant tumorsRas-driven oncogenesisCarcinogenesis in vivoSubstrate of PKAConstitutively activating mutationAppendix cancerPan-cancer analysisActivation of signalingPatient sequencing dataBenign tumorsCell carcinoma