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 lethalityMetformin 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