2020
WNT Signaling Driven by R-spondin 1 and LGR6 in High-grade Serous Ovarian Cancer
LEE S, JUN J, KIM W, TAMAYO P, HOWELL S. WNT Signaling Driven by R-spondin 1 and LGR6 in High-grade Serous Ovarian Cancer. Anticancer Research 2020, 40: 6017-6028. PMID: 33109540, PMCID: PMC9312105, DOI: 10.21873/anticanres.14623.Peer-Reviewed Original ResearchConceptsHigh-grade serous ovarian cancerGene set enrichment analysisSerous ovarian cancerWnt signalingOvarian surfaceExpression of RSPO1Gene set enrichment analysis methodRNA-seq dataControl cell fateR-spondinOvarian cancerAnalysis of genesNormal tissuesWnt signaling pathwayHuman Protein AtlasAdjacent genesImpact overall survivalLevel of expressionRNA-seqAssociation studiesCell fateCopy numberGO pathwaysAnalysis of TCGAEnrichment analysisMesenchymal 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 immortality
2018
An alternative splicing switch in FLNB promotes the mesenchymal cell state in human breast cancer
Li J, Choi P, Chaffer C, Labella K, Hwang J, Giacomelli A, Kim J, Ilic N, Doench J, Ly S, Dai C, Hagel K, Hong A, Gjoerup O, Goel S, Ge J, Root D, Zhao J, Brooks A, Weinberg R, Hahn W. An alternative splicing switch in FLNB promotes the mesenchymal cell state in human breast cancer. ELife 2018, 7: e37184. PMID: 30059005, PMCID: PMC6103745, DOI: 10.7554/elife.37184.Peer-Reviewed Original ResearchMeSH KeywordsAlternative SplicingAnimalsBase SequenceBreast NeoplasmsCell Line, TumorEpithelial-Mesenchymal TransitionExonsFemaleFilaminsGene Expression Regulation, NeoplasticGenome, HumanHumansHyaluronan ReceptorsMesenchymal Stem CellsMice, NudeNeoplasm ProteinsOpen Reading FramesProtein IsoformsReproducibility of ResultsRNA, MessengerRNA-Binding ProteinsConceptsEpithelial-to-mesenchymal transitionAlternative splicing of mRNA precursorsMesenchymal cell stateSplicing of mRNA precursorsCell statesRNA-binding proteinsAlternative splicing switchDysregulation of splicingBreast cancer patient samplesEMT gene signatureRegulation of epithelial-to-mesenchymal transitionCancer patient samplesInduce epithelial-to-mesenchymal transitionFOXC1 transcription factorRNA-seqAlternative splicingExpression screeningMRNA precursorsRegulating tumor cell plasticityRegulatory stepTranscription factorsSplicing switchProtein productionDiverse functionsIncreased tumorigenicityTumor innate immunity primed by specific interferon-stimulated endogenous retroviruses
Cañadas I, Thummalapalli R, Kim J, Kitajima S, Jenkins R, Christensen C, Campisi M, Kuang Y, Zhang Y, Gjini E, Zhang G, Tian T, Sen D, Miao D, Imamura Y, Thai T, Piel B, Terai H, Aref A, Hagan T, Koyama S, Watanabe M, Baba H, Adeni A, Lydon C, Tamayo P, Wei Z, Herlyn M, Barbie T, Uppaluri R, Sholl L, Sicinska E, Sands J, Rodig S, Wong K, Paweletz C, Watanabe H, Barbie D. Tumor innate immunity primed by specific interferon-stimulated endogenous retroviruses. Nature Medicine 2018, 24: 1143-1150. PMID: 30038220, PMCID: PMC6082722, DOI: 10.1038/s41591-018-0116-5.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorEndogenous RetrovirusesGene Expression Regulation, NeoplasticHumansImmunity, InnateInterferonsMice, NudeNeoplasmsRNA, AntisenseConceptsInnate immune signalingSmall cell lung cancerEndogenous retrovirusesCell lung cancerPro-tumorigenic cytokinesImmune signalingAnalysis of cell linesCancer immunotherapyMesenchymal cell stateIFN-gTumor subpopulationsLung cancerLong terminal repeatHuman tumorsSPARC expressionMesenchymal markersTumorBi-directional transcriptionChromatin-modifying enzymesSTAT1 signalingCell linesCancerInnate immunityInducible SPARCS expressionGene promoter
2017
Decomposing Oncogenic Transcriptional Signatures to Generate Maps of Divergent Cellular States
Kim J, Abudayyeh O, Yeerna H, Yeang C, Stewart M, Jenkins R, Kitajima S, Konieczkowski D, Medetgul-Ernar K, Cavazos T, Mah C, Ting S, Van Allen E, Cohen O, Mcdermott J, Damato E, Aguirre A, Liang J, Liberzon A, Alexe G, Doench J, Ghandi M, Vazquez F, Weir B, Tsherniak A, Subramanian A, Meneses-Cime K, Park J, Clemons P, Garraway L, Thomas D, Boehm J, Barbie D, Hahn W, Mesirov J, Tamayo P. Decomposing Oncogenic Transcriptional Signatures to Generate Maps of Divergent Cellular States. Cell Systems 2017, 5: 105-118.e9. PMID: 28837809, PMCID: PMC5639711, DOI: 10.1016/j.cels.2017.08.002.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorCell Line, TumorGene Expression ProfilingGene Expression Regulation, NeoplasticGenes, rasGenomeHumansMAP Kinase Signaling SystemNeoplasmsPrecision MedicineConceptsCellular statesActivated downstream of RasDownstream of RasGenomic hallmarksIndividual tumor samplesCancer genomesRas pathwayPrecision medicine paradigmPharmacological perturbationsGenetic alterationsFunctional consequencesTranscriptional signatureSystematic sequenceReference mapEffective disease modelsOncogenic alterationsRasComplex landscapeTumor samplesDisease modelsTherapeutic strategiesMedicine paradigmGenomeAlterationsFunctional state
2014
A Melanoma Cell State Distinction Influences Sensitivity to MAPK Pathway Inhibitors
Konieczkowski D, Johannessen C, Abudayyeh O, Kim J, Cooper Z, Piris A, Frederick D, Barzily-Rokni M, Straussman R, Haq R, Fisher D, Mesirov J, Hahn W, Flaherty K, Wargo J, Tamayo P, Garraway L. A Melanoma Cell State Distinction Influences Sensitivity to MAPK Pathway Inhibitors. Cancer Discovery 2014, 4: 816-827. PMID: 24771846, PMCID: PMC4154497, DOI: 10.1158/2159-8290.cd-13-0424.Peer-Reviewed Original ResearchMeSH KeywordsAnilidesBenzimidazolesBenzocycloheptenesCell Line, TumorCells, CulturedDrug Resistance, NeoplasmGene Expression Regulation, NeoplasticHepatocyte Growth FactorHumansIndolesMAP Kinase Signaling SystemMelanocytesMelanomaMicrophthalmia-Associated Transcription FactorNF-kappa B p50 SubunitProtein Kinase InhibitorsProto-Oncogene Proteins B-rafProto-Oncogene Proteins c-metPyridinesQuinolinesSulfonamidesTriazolesConceptsBRAF(V600)-mutant melanomaMAPK pathway inhibitorsNF-kB activationPathway inhibitorNF-kBMelanocyte lineage transcription factor MITFCell linesDrug-sensitive cell linesResistance to MAPK pathway inhibitorsMITF expressionReceptor tyrosine kinase AXLTranscription factor MITFTyrosine kinase AXLResistance marker genesResistant cell linesNF-kB signalingResistant to inhibitionClinical benefitPatient biopsiesMEK inhibitorsTranscriptional profilesOncogenic BRAF(V600EDrug resistanceInhibitor sensitivityCell states