2016
Phosphoinositide 3-kinase inhibitors induce DNA damage through nucleoside depletion
Juvekar A, Hu H, Yadegarynia S, Lyssiotis C, Ullas S, Lien E, Bellinger G, Son J, Hok R, Seth P, Daly M, Kim B, Scully R, Asara J, Cantley L, Wulf G. Phosphoinositide 3-kinase inhibitors induce DNA damage through nucleoside depletion. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: e4338-e4347. PMID: 27402769, PMCID: PMC4968752, DOI: 10.1073/pnas.1522223113.Peer-Reviewed Original ResearchMeSH KeywordsAminopyridinesAnimalsAntineoplastic Combined Chemotherapy ProtocolsCell Line, TumorCell ProliferationDNA DamageDNA, NeoplasmFemaleHumansMice, Inbred C57BLMice, Inbred NODMice, KnockoutMice, SCIDMorpholinesNucleosidesPhosphatidylinositol 3-KinasePhosphoinositide-3 Kinase InhibitorsPoly(ADP-ribose) Polymerase InhibitorsTriple Negative Breast NeoplasmsConceptsDNA damagePI3KDNA synthesisNonoxidative pentose phosphate pathwayProtein kinase AktPentose phosphate pathwayKinase AktPI3K inhibitor BKM120DNA repairPI3K inhibitorsPI3K inhibitionPhosphate pathwayCarbon flux studiesCell deathNucleotide synthesisNucleotide triphosphatesMutational backgroundK inhibitionK inhibitorsGenetic aberrationsMouse modelPARP inhibitionInhibitorsBRCA1Triple-negative breast cancer
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 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 defectMetabolismOutcomesProliferationCellsTumorsIdentification 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
2008
ErbB3 is required for ductal morphogenesis in the mouse mammary gland
Jackson-Fisher AJ, Bellinger G, Breindel JL, Tavassoli FA, Booth CJ, Duong JK, Stern DF. ErbB3 is required for ductal morphogenesis in the mouse mammary gland. Breast Cancer Research 2008, 10: r96. PMID: 19019207, PMCID: PMC2656891, DOI: 10.1186/bcr2198.Peer-Reviewed Original ResearchConceptsTerminal end budsMammary fat padEnd budsMammary budBreast cancerFat padDuctal outgrowthMammary glandHER2/neuHuman breast cancerSmooth muscle actinNormal mammary glandSections of glandsMammary ductal treeMouse mammary gland developmentMammary gland developmentErbB3 functionMouse mammary glandRole of ErbB3Lobuloalveolar developmentEpithelial areaErbB2/HER2/NeuPredictive valueMuscle actinTherapeutic resistance