2019
Cooperative adaptation to therapy (CAT) confers resistance in heterogeneous non-small cell lung cancer
Craig M, Kaveh K, Woosley A, Brown AS, Goldman D, Eton E, Mehta RM, Dhawan A, Arai K, Rahman MM, Chen S, Nowak MA, Goldman A. Cooperative adaptation to therapy (CAT) confers resistance in heterogeneous non-small cell lung cancer. PLOS Computational Biology 2019, 15: e1007278. PMID: 31449515, PMCID: PMC6709889, DOI: 10.1371/journal.pcbi.1007278.Peer-Reviewed Original ResearchMeSH KeywordsAdaptation, PhysiologicalCarcinoma, Non-Small-Cell LungCell Line, TumorCell ProliferationCoculture TechniquesComputational BiologyComputer SimulationCRISPR-Cas SystemsDEAD-box RNA HelicasesDrug Resistance, MultipleDrug Resistance, NeoplasmHumansLung NeoplasmsModels, BiologicalMutationRibonuclease IIIConceptsCancer cellsCell state transitionsWild-type cellsCooperative adaptationNon-small cell lung cancer cellsInterspecies competitionCell lung cancer cellsCRISPR/Drug-sensitive cellsLung cancer cellsNSCLC patient samplesDruggable targetsDrug pressureMutantsFlow cytometry dataPhenotypic heterogeneitySensitive cells
2015
Genome-wide CRISPR Screen in a Mouse Model of Tumor Growth and Metastasis
Chen S, Sanjana NE, Zheng K, Shalem O, Lee K, Shi X, Scott DA, Song J, Pan JQ, Weissleder R, Lee H, Zhang F, Sharp PA. Genome-wide CRISPR Screen in a Mouse Model of Tumor Growth and Metastasis. Cell 2015, 160: 1246-1260. PMID: 25748654, PMCID: PMC4380877, DOI: 10.1016/j.cell.2015.02.038.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarcinoma, Non-Small-Cell LungCRISPR-Cas SystemsGene Knockout TechniquesGenome-Wide Association StudyHumansLung NeoplasmsMiceNeoplasm MetastasisRNA, Guide, CRISPR-Cas SystemsConceptsSingle guide RNAsGenome-wide CRISPR screenGenome-scale libraryCRISPR/Cas9-mediated lossLate-stage primary tumorsEffects of mutationsGenetic screenTumor growthCRISPR screensFunction screenMouse cancer cell linesCancer evolutionGene phenotypeDiverse phenotypesFunction mutationsCancer cell linesGenesCell linesPrimary screenCell poolSpecific lossPrimary tumor growthSmall poolMutationsPhenotype
2014
Global microRNA depletion suppresses tumor angiogenesis
Chen S, Xue Y, Wu X, Le C, Bhutkar A, Bell EL, Zhang F, Langer R, Sharp PA. Global microRNA depletion suppresses tumor angiogenesis. Genes & Development 2014, 28: 1054-1067. PMID: 24788094, PMCID: PMC4035535, DOI: 10.1101/gad.239681.114.Peer-Reviewed Original ResearchConceptsUntranslated regionCRISPR/Multiplexed CRISPR/HIF transcriptional activityHypoxia-inducible factor-1Tumor angiogenesisMicroRNA-binding sitesGenome engineeringExpression profilingTranscriptional activityHypoxia responseBalance of angiogenesisHIF transcriptionMicroRNA deficiencyMicroRNAsFIH1Factor 1Angiogenesis genesDeficient angiogenesisAngiogenesisVEGF productionTranscription