2022
Pyruvate kinase M1 suppresses development and progression of prostate adenocarcinoma
Davidson S, Schmidt D, Heyman J, O'Brien J, Liu A, Israelsen W, Dayton T, Sehgal R, Bronson R, Freinkman E, Mak H, Fanelli G, Malstrom S, Bellinger G, Carracedo A, Pandolfi P, Courtney K, Jha A, DePinho R, Horner J, Thomas C, Cantley L, Loda M, Vander Heiden M. Pyruvate kinase M1 suppresses development and progression of prostate adenocarcinoma. Cancer Research 2022, 82: 2403-2416. PMID: 35584006, PMCID: PMC9256808, DOI: 10.1158/0008-5472.can-21-2352.Peer-Reviewed Original Research
2014
Pyruvate Kinase Isoform Expression Alters Nucleotide Synthesis to Impact Cell Proliferation
Lunt S, Muralidhar V, Hosios A, Israelsen W, Gui D, Newhouse L, Ogrodzinski M, Hecht V, Xu K, Acevedo P, Hollern D, Bellinger G, Dayton T, Christen S, Elia I, Dinh A, Stephanopoulos G, Manalis S, Yaffe M, Andrechek E, Fendt S, Vander Heiden M. Pyruvate Kinase Isoform Expression Alters Nucleotide Synthesis to Impact Cell Proliferation. Molecular Cell 2014, 57: 95-107. PMID: 25482511, PMCID: PMC4289430, DOI: 10.1016/j.molcel.2014.10.027.Peer-Reviewed Original ResearchConceptsProliferation arrestPKM1 expressionCell proliferationImpacts cell proliferationPrimary cellsPyruvate kinase isoformsNormal cell proliferationPKM2 lossGene expressionKinase isoformsCell cycleCell differentiationNucleotide levelCell growthNucleotide synthesisPKM2 deletionExpression impairsPKM2DNA synthesisMetabolic stateExpressionDeletionProliferationCellsArrest
2013
PKM2 Isoform-Specific Deletion Reveals a Differential Requirement for Pyruvate Kinase in Tumor Cells
Israelsen WJ, Dayton TL, Davidson SM, Fiske BP, Hosios AM, Bellinger G, Li J, Yu Y, Sasaki M, Horner JW, Burga LN, Xie J, Jurczak MJ, DePinho RA, Clish CB, Jacks T, Kibbey RG, Wulf GM, Di Vizio D, Mills GB, Cantley LC, Vander Heiden M. PKM2 Isoform-Specific Deletion Reveals a Differential Requirement for Pyruvate Kinase in Tumor Cells. Cell 2013, 155: 397-409. PMID: 24120138, PMCID: PMC3850755, DOI: 10.1016/j.cell.2013.09.025.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceBreast NeoplasmsExonsFemaleGene DeletionGene Knockout TechniquesHeterograftsHumansIsoenzymesMammary Neoplasms, ExperimentalMiceMice, Inbred C57BLModels, MolecularMolecular Sequence DataMutagenesisMutationNeoplasm MetastasisNeoplasm TransplantationPyruvate KinaseRNA SplicingConceptsTumor cellsPKM2 expressionPKM1 expressionTumor formationMammary tumor formationTumor cell proliferationPyruvate kinase M2 isoformPyruvate kinase expressionBreast cancerNull tumorsHuman tumorsTumorsKinase expressionCell proliferationCell populationsPKM2 deletionPKM2 activityCancerPKM2Anabolic metabolismMetabolic requirementsPyruvate kinaseM2 isoformDifferent metabolic requirements
2011
Inhibition of Pyruvate Kinase M2 by Reactive Oxygen Species Contributes to Cellular Antioxidant Responses
Anastasiou D, Poulogiannis G, Asara J, Boxer M, Jiang J, Shen M, Bellinger G, Sasaki A, Locasale J, Auld D, Thomas C, Vander Heiden M, Cantley L. Inhibition of Pyruvate Kinase M2 by Reactive Oxygen Species Contributes to Cellular Antioxidant Responses. Science 2011, 334: 1278-1283. PMID: 22052977, PMCID: PMC3471535, DOI: 10.1126/science.1211485.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcysteineAmino Acid SubstitutionAnimalsAntioxidantsCell LineCell Line, TumorCell SurvivalCysteineDiamideEnzyme ActivatorsGlucoseGlutathioneHumansMiceMice, NudeMutant ProteinsNeoplasm TransplantationNeoplasms, ExperimentalOxidation-ReductionOxidative StressPentose Phosphate PathwayProtein SubunitsPyruvate KinaseReactive Oxygen SpeciesTransplantation, HeterologousConceptsPyruvate kinase M2Lung cancer cellsCancer cellsKinase M2Human lung cancer cellsReactive oxygen species contributesInhibition of PKM2Intracellular reactive oxygen species (ROS) concentrationCancer cell survivalCellular antioxidant responseGlycolytic enzyme pyruvate kinase M2Acute increaseXenograft modelReactive oxygen species concentrationMetabolic changesOxidative stressTumor formationGlucose fluxCell survivalIntracellular concentrationAntioxidant responseInhibitionCellsOxygen species concentrationROS