2021
Developmental partitioning of SYK and ZAP70 prevents autoimmunity and cancer
Sadras T, Martin M, Kume K, Robinson ME, Saravanakumar S, Lenz G, Chen Z, Song JY, Siddiqi T, Oksa L, Knapp AM, Cutler J, Cosgun KN, Klemm L, Ecker V, Winchester J, Ghergus D, Soulas-Sprauel P, Kiefer F, Heisterkamp N, Pandey A, Ngo V, Wang L, Jumaa H, Buchner M, Ruland J, Chan WC, Meffre E, Martin T, Müschen M. Developmental partitioning of SYK and ZAP70 prevents autoimmunity and cancer. Molecular Cell 2021, 81: 2094-2111.e9. PMID: 33878293, PMCID: PMC8239336, DOI: 10.1016/j.molcel.2021.03.043.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CD19AutoimmunityB-LymphocytesCalciumCell DifferentiationCell Transformation, NeoplasticEnzyme ActivationHumansImmune ToleranceLymphoma, B-CellMiceModels, GeneticNeoplasm ProteinsNeoplasmsNFATC Transcription FactorsPhosphatidylinositol 3-KinasesProtein BindingReceptors, Antigen, B-CellSignal TransductionSyk KinaseZAP-70 Protein-Tyrosine KinasePON2 subverts metabolic gatekeeper functions in B cells to promote leukemogenesis
Pan L, Hong C, Chan LN, Xiao G, Malvi P, Robinson ME, Geng H, Reddy ST, Lee J, Khairnar V, Cosgun KN, Xu L, Kume K, Sadras T, Wang S, Wajapeyee N, Müschen M. PON2 subverts metabolic gatekeeper functions in B cells to promote leukemogenesis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2016553118. PMID: 33531346, PMCID: PMC7896313, DOI: 10.1073/pnas.2016553118.Peer-Reviewed Original ResearchConceptsTransplant recipient miceDNA double-strand breaksNormal B cell developmentDouble-strand breaksB cell developmentGenetic deletionB cellsLymphoid transcription factorsGlucose transporter GLUT1Gatekeeper functionGlucose uptakeRecipient miceTranscription factorsSomatic recombinationSynthetic lethalityB-cell acute lymphoblastic leukemiaCell developmentMetabolic gatekeeperRefractory B-ALLDeficient murineCell acute lymphoblastic leukemiaPoor clinical outcomeCell typesAcute lymphoblastic leukemiaGlucose transport
2020
IFITM3 functions as a PIP3 scaffold to amplify PI3K signalling in B cells
Lee J, Robinson ME, Ma N, Artadji D, Ahmed MA, Xiao G, Sadras T, Deb G, Winchester J, Cosgun KN, Geng H, Chan LN, Kume K, Miettinen TP, Zhang Y, Nix MA, Klemm L, Chen CW, Chen J, Khairnar V, Wiita AP, Thomas-Tikhonenko A, Farzan M, Jung JU, Weinstock DM, Manalis SR, Diamond MS, Vaidehi N, Müschen M. IFITM3 functions as a PIP3 scaffold to amplify PI3K signalling in B cells. Nature 2020, 588: 491-497. PMID: 33149299, PMCID: PMC8087162, DOI: 10.1038/s41586-020-2884-6.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CD19B-LymphocytesCell Transformation, NeoplasticFemaleGerminal CenterHumansIntegrinsMembrane MicrodomainsMembrane ProteinsMiceMice, Inbred C57BLMice, Inbred NODModels, MolecularPhosphatidylinositol 3-KinasesPhosphatidylinositol PhosphatesPhosphorylationReceptors, Antigen, B-CellRNA-Binding ProteinsSignal TransductionConceptsPI3KCell leukemiaAntiviral effector functionsAntigen-specific antibodiesInterferon-induced transmembrane proteinsIFITM3 functionDevelopment of leukemiaCell surfacePoor outcomeOncogenic PI3KClinical cohortEffector functionsGerminal centersMouse modelB cellsExpression of IFITM3Malignant transformationAccumulation of PIP3PI3K signalsCell receptorNormal numbersLeukemiaDefective expressionEndosomal proteinIFITM3Signalling input from divergent pathways subverts B cell transformation
Chan LN, Murakami MA, Robinson ME, Caeser R, Sadras T, Lee J, Cosgun KN, Kume K, Khairnar V, Xiao G, Ahmed MA, Aghania E, Deb G, Hurtz C, Shojaee S, Hong C, Pölönen P, Nix MA, Chen Z, Chen CW, Chen J, Vogt A, Heinäniemi M, Lohi O, Wiita AP, Izraeli S, Geng H, Weinstock DM, Müschen M. Signalling input from divergent pathways subverts B cell transformation. Nature 2020, 583: 845-851. PMID: 32699415, PMCID: PMC7394729, DOI: 10.1038/s41586-020-2513-4.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsB-LymphocytesCell Line, TumorCell Transformation, NeoplasticEnzyme ActivationExtracellular Signal-Regulated MAP KinasesFemaleHumansLeukemia, B-CellMiceProtein Tyrosine Phosphatase, Non-Receptor Type 6Proto-Oncogene Proteins c-bcl-6Proto-Oncogene Proteins c-mycSignal TransductionSTAT5 Transcription FactorConceptsPre-B cell receptorPrincipal oncogenic driverDivergent pathwaysSignal transduction proteinsPro-B cell stageSingle-cell mutationTranscription factor MYCOncogenic driversDivergent signaling pathwaysSingle oncogenic pathwayCentral oncogenic driverMore mature cellsGenetic reactivationTranscriptional programsB-cell transformationProtein kinasePathway componentsERK activationIndividual mutationsOncogenic STAT5Signaling pathwaysCell transformationCytokine receptorsGenetic lesionsDivergent circuits
2017
Inhibition of PI3K suppresses propagation of drug-tolerant cancer cell subpopulations enriched by 5-fluorouracil
Ishida K, Ito C, Ohmori Y, Kume K, Sato KA, Koizumi Y, Konta A, Iwaya T, Nukatsuka M, Kobunai T, Takechi T, Nishizuka SS. Inhibition of PI3K suppresses propagation of drug-tolerant cancer cell subpopulations enriched by 5-fluorouracil. Scientific Reports 2017, 7: 2262. PMID: 28536445, PMCID: PMC5442158, DOI: 10.1038/s41598-017-02548-9.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntimetabolites, AntineoplasticCell Line, TumorCell ProliferationClass I Phosphatidylinositol 3-KinasesCodonDisease Models, AnimalDose-Response Relationship, DrugDrug Resistance, NeoplasmFluorouracilGenetic VariationHeterograftsHumansMiceNeoplasmsPhenotypePhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPhosphorylationProteomeProteomicsRibosomal Protein S6 Kinases, 90-kDaSignal TransductionConceptsOrthotopic xenograftsCancer cell subpopulationsCell subpopulationsGastric cancer cell line MKN45Gastric cancer chemotherapyRibosomal S6 kinase phosphorylationPI3K inhibitorsDisease relapseSequential administrationS6 kinase phosphorylationNude miceTumor propagationCancer chemotherapyK inhibitorsXenograftsPI3KChemotherapyRelapseTolerant subpopulationSubpopulationsKinase phosphorylationAdministrationCellsPhosphorylated phosphatidylinositidesMice
2016
α-Amanitin Restrains Cancer Relapse from Drug-Tolerant Cell Subpopulations via TAF15
Kume K, Ikeda M, Miura S, Ito K, Sato KA, Ohmori Y, Endo F, Katagiri H, Ishida K, Ito C, Iwaya T, Nishizuka SS. α-Amanitin Restrains Cancer Relapse from Drug-Tolerant Cell Subpopulations via TAF15. Scientific Reports 2016, 6: 25895. PMID: 27181033, PMCID: PMC4867652, DOI: 10.1038/srep25895.Peer-Reviewed Original ResearchMeSH KeywordsAlpha-AmanitinAnimalsCell Line, TumorCisplatinDown-RegulationDrug ResistanceEnzyme InhibitorsGene Expression Regulation, NeoplasticHCT116 CellsHeLa CellsHT29 CellsHumansMCF-7 CellsMicePeritoneal NeoplasmsProteomicsSecondary PreventionTATA-Binding Protein Associated FactorsTranscription, GeneticXenograft Model Antitumor AssaysConceptsΑ-amanitinRNA polymerase II inhibitorProtein expression patternsTranscriptional machineryRNA processingProteomic characterizationFunctional screeningTranscriptional levelExpression patternsTAF15II inhibitorsCancer cellsSubstantial frequencyDTC formationCancer relapseCell subpopulationsSubpopulationsTranscriptionMouse modelMachineryRNAPresence of drugsStemnessColoniesExpression
2015
A Distinct Subpopulation of Bone Marrow Mesenchymal Stem Cells, Muse Cells, Directly Commit to the Replacement of Liver Components
Katagiri H, Kushida Y, Nojima M, Kuroda Y, Wakao S, Ishida K, Endo F, Kume K, Takahara T, Nitta H, Tsuda H, Dezawa M, Nishizuka SS. A Distinct Subpopulation of Bone Marrow Mesenchymal Stem Cells, Muse Cells, Directly Commit to the Replacement of Liver Components. American Journal Of Transplantation 2015, 16: 468-483. PMID: 26663569, DOI: 10.1111/ajt.13537.Peer-Reviewed Original ResearchConceptsLiver componentsBone marrow mesenchymal stem cellsMarrow mesenchymal stem cellsLiver regenerationBM-MSCsMuse cellsMesenchymal stem cellsLiving-donor liver transplantationSinusoidal endothelial cellsMultilineage-differentiating stress-enduring (Muse) cellsPartial hepatectomy modelStem cellsGraft liverLiver transplantationPolymerase chain reactionCell involvementImmunodeficient miceKupffer cellsSinusoidal cellsPeriportal areasExtrahepatic originHepatectomy modelSpecific subpopulationsEndothelial cellsProgenitor markers