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