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
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 lethalityIdentification of CDCP1 as a hypoxia-inducible factor 2α (HIF-2α) target gene that is associated with survival in clear cell renal cell carcinoma patients
Emerling B, Benes C, Poulogiannis G, Bell E, Courtney K, Liu H, Choo-Wing R, Bellinger G, Tsukazawa K, Brown V, Signoretti S, Soltoff S, Cantley L. Identification of CDCP1 as a hypoxia-inducible factor 2α (HIF-2α) target gene that is associated with survival in clear cell renal cell carcinoma patients. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 3483-3488. PMID: 23378636, PMCID: PMC3587206, DOI: 10.1073/pnas.1222435110.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDAntigens, NeoplasmBasic Helix-Loop-Helix Transcription FactorsCarcinoma, Renal CellCell Adhesion MoleculesCell HypoxiaCell Line, TumorCell ProliferationGenes, NeoplasmHumansKidney NeoplasmsMiceMice, NudeNeoplasm ProteinsSignal TransductionSrc-Family KinasesSurvival AnalysisXenograft Model Antitumor AssaysConceptsCUB domain-containing protein 1CDCP1 expressionHypoxia-inducible factorTyrosine phosphorylationTarget genesDomain-containing protein 1HIF-2α target genesCancer cell metastasisCancer cell migrationTransmembrane proteinClear cell renal cell carcinoma patientsRenal cell carcinoma patientsShRNA knockdownClear cell renal cell carcinomaCell migrationCell carcinoma patientsCell metastasisCell renal cell carcinomaTumors of patientsRenal cell carcinomaProtein 1Stem cellsPotential therapeutic targetTissue microarray samplesCancer metastasis