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 ResearchConceptsInnate 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