2021
Protein Phosphatase 2A as a Therapeutic Target in Small Cell Lung Cancer
Mirzapoiazova T, Xiao G, Mambetsariev B, Nasser MW, Miaou E, Singhal SS, Srivastava S, Mambetsariev I, Nelson MS, Nam A, Behal A, Arvanitis LD, Atri P, Muschen M, Tissot FLH, Miser J, Kovach JS, Sattler M, Batra SK, Kulkarni P, Salgia R. Protein Phosphatase 2A as a Therapeutic Target in Small Cell Lung Cancer. Molecular Cancer Therapeutics 2021, 20: 1820-1835. PMID: 34253596, PMCID: PMC8722383, DOI: 10.1158/1535-7163.mct-21-0013.Peer-Reviewed Original ResearchConceptsProtein phosphatase 2APhosphatase 2ASerine/threonine phosphataseDNA damage responseRegulation of apoptosisSmall molecule inhibitorsGlycolytic ATP productionThreonine phosphataseTwo-dimensional cultureLB100ATP productionMolecule inhibitorsPP2AThree-dimensional spheroid modelEndothelial cell monolayersGlucose uptakeCell viabilitySCLC cellsTherapeutic targetApoptosisCell monolayersMass spectrometrySpheroid modelTumor spheroidsCells
2016
PP2A Balances Glucose Metabolism and Foxo Activation to Maintain Cellular Redox Homeostasis in Acute Lymphoblastic Leukemia
Xiao G, Chen Z, Daniel B, Chan L, Geng H, Jiang X, Müschen M. PP2A Balances Glucose Metabolism and Foxo Activation to Maintain Cellular Redox Homeostasis in Acute Lymphoblastic Leukemia. Blood 2016, 128: 1056. DOI: 10.1182/blood.v128.22.1056.1056.Peer-Reviewed Original ResearchLineage-specific rolesPro-survival roleLB-100PP2A subunitsRedox homeostasisH2AX phosphorylationUnexpected rolePI3K-AktFunction of PP2AProtein phosphatase 2ACellular redox homeostasisSer/ThrCatalytic subunit CAnti-oxidant gene expressionS6 ribosomal proteinHigh glycolytic fluxRescue effectGrowth competition assaysLeukemia cellsPentose phosphate pathway fluxHigher reactive oxygen species (ROS) levelsReduced cell growthPP2A functionSmall molecule inhibitorsFOXO factorsPhosphorylation of a constrained azacyclic FTY720 analog enhances anti-leukemic activity without inducing S1P receptor activation
McCracken A, McMonigle R, Tessier J, Fransson R, Perryman M, Chen B, Keebaugh A, Selwan E, Barr S, Kim S, Roy S, Liu G, Fallegger D, Sernissi L, Brandt C, Moitessier N, Snider A, Clare S, Müschen M, Huwiler A, Kleinman M, Hanessian S, Edinger A. Phosphorylation of a constrained azacyclic FTY720 analog enhances anti-leukemic activity without inducing S1P receptor activation. Leukemia 2016, 31: 669-677. PMID: 27573555, PMCID: PMC5332311, DOI: 10.1038/leu.2016.244.Peer-Reviewed Original ResearchConceptsS1P receptor activationAnti-leukemic actionProtein phosphatase 2APro-apoptotic targetsPhosphatase 2ASphingosine kinase 2Efficient phosphorylationGenetic approachesReceptor activationKinase 2Nutrient accessChemical biologyPhosphorylationTight inverse correlationDistinct mechanismsS1P receptorsAnti-leukemic activityNovel therapeutic approachesLeukemia progressionReceptor activityMRNA expressionAnti-leukemic agentsActivationEnhanced potencyBiology
2015
PP2A Is Required for B Cell Survival and Represents a Therapeutic Target in Acute Lymphoblastic Leukemia
Gang X, Geng H, Chan L, Chen Z, Jiang X, Muschen M. PP2A Is Required for B Cell Survival and Represents a Therapeutic Target in Acute Lymphoblastic Leukemia. Blood 2015, 126: 902. DOI: 10.1182/blood.v126.23.902.902.Peer-Reviewed Original ResearchLB-100B cell survivalCell deathH2AX phosphorylationSer/Thr protein phosphatase 2ACell lineagesCell-specific vulnerabilityCell survivalFunction of PP2AEarly B cell developmentProtein phosphatase 2AB-cell lineageCatalytic subunit CGlycolytic fluxAnti-oxidant gene expressionTumor suppressor functionRapid cell deathS6 ribosomal proteinHigh glycolytic fluxB cell developmentImportant tumor suppressorPro-survival roleHigher reactive oxygen species (ROS) levelsCre-mediated deletionPP2A subunits
2014
Divergent Lineage-Specific Functions of PP2A in Chronic Phase CML and Lymphoid Blast Crisis
Xiao G, Geng H, Chan L, Chen Z, Muschen M. Divergent Lineage-Specific Functions of PP2A in Chronic Phase CML and Lymphoid Blast Crisis. Blood 2014, 124: 3128. DOI: 10.1182/blood.v124.21.3128.3128.Peer-Reviewed Original ResearchFunction of PP2ACell lineagesB cell developmentB-cell lineageSer/Thr phosphataseCell developmentPI3K-AktEarly B cell developmentProtein phosphatase 2ALineage-specific functionsNormal B cell developmentChronic phase chronic myeloid leukemiaLineage-specific requirementGlycolytic fluxPre-B cell receptor checkpointMyeloid lineagePhase chronic myeloid leukemiaChronic myeloid leukemiaRegulation of AktS6 ribosomal proteinHigh glycolytic fluxRapid cell deathLymphoid blast crisisImportant tumor suppressorColony formation capability