2013
Depletion of a Putatively Druggable Class of Phosphatidylinositol Kinases Inhibits Growth of p53-Null Tumors
Emerling B, Hurov J, Poulogiannis G, Tsukazawa K, Choo-Wing R, Wulf G, Bell E, Shim H, Lamia K, Rameh L, Bellinger G, Sasaki A, Asara J, Yuan X, Bullock A, DeNicola G, Song J, Brown V, Signoretti S, Cantley L. Depletion of a Putatively Druggable Class of Phosphatidylinositol Kinases Inhibits Growth of p53-Null Tumors. Cell 2013, 155: 844-857. PMID: 24209622, PMCID: PMC4070383, DOI: 10.1016/j.cell.2013.09.057.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBreast NeoplasmsCell Line, TumorCell ProliferationCell RespirationCellular SenescenceEmbryo, MammalianGene Knockdown TechniquesGenes, LethalHeterograftsHumansMiceNeoplasm TransplantationPhosphotransferases (Alcohol Group Acceptor)Reactive Oxygen SpeciesSignal TransductionTumor Suppressor Protein p53ConceptsReactive oxygen speciesP53-null tumorsBreast cancer cell linesCancer cell linesBreast cancerType 2Druggable classesAbsence of p53Tumor formationInhibits growthCell linesCancerHomozygous deletionMiceTP53Oxygen speciesP53Enhanced levelsHigh levelsDramatic reductionXenograftsLittermatesTumorsSynthetic lethality
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