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 tumorigenicity
2017
Abstract 5020: A genome-scale ORF screen reveals an alternative splicing program that regulates mesenchymal and stem-like cell states in breast cancer
Li J, Choi P, Chaffer C, Labella K, Kim J, Doench J, Dai C, Giacomelli A, Ly S, Hwang J, Hong A, Ilic N, Gjoerup O, Meyerson M, Brooks A, Weinberg R, Hahn W. Abstract 5020: A genome-scale ORF screen reveals an alternative splicing program that regulates mesenchymal and stem-like cell states in breast cancer. Cancer Research 2017, 77: 5020-5020. DOI: 10.1158/1538-7445.am2017-5020.Peer-Reviewed Original ResearchAlternative splicing programFilamin BSplicing factorsGene set enrichment analysisAlternative splicingCell statesSplicing programCD44 cell surface markersRegulation of EMTShort isoformStem-like stateDownstream targetsStem cell fate determinationCell fate determinationRNA splicing factorsHuman mammary epithelial cellsBreast cancer patient samplesMammary epithelial cellsBreast cancer cell linesRNA sequencing analysisTumor formation in vivoAssociated with stem cell propertiesBasal-like breast cancerCancer patient samplesStem-like traits
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