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 requirementsMetformin Decreases Glucose Oxidation and Increases the Dependency of Prostate Cancer Cells on Reductive Glutamine Metabolism
Fendt S, Bell E, Keibler M, Davidson S, Wirth G, Fiske B, Mayers J, Schwab M, Bellinger G, Csibi A, Patnaik A, Blouin M, Cantley L, Guarente L, Blenis J, Pollak M, Olumi A, Vander Heiden M, Stephanopoulos G. Metformin Decreases Glucose Oxidation and Increases the Dependency of Prostate Cancer Cells on Reductive Glutamine Metabolism. Cancer Research 2013, 73: 4429-4438. PMID: 23687346, PMCID: PMC3930683, DOI: 10.1158/0008-5472.can-13-0080.Peer-Reviewed Original ResearchConceptsProstate cancer cellsProstate cancerCancer cellsGlutamine metabolismReductive glutamine metabolismCancer cell proliferationPresence of metforminCancer cell linesGlucose oxidationCancer outcomesMouse modelAttenuated proliferationMetforminEpidemiology studiesCancerGlutamine anaplerosisCell proliferationPatientsCell linesProliferative defectMetabolismOutcomesProliferationCellsTumors