1. HanahanD, WeinbergRA. Hallmarks of cancer: the next generation. Cell 2011;144:646-74.
2. WarburgO. On the origin of cancer cells. Science 1956;123:309-14.
3. Vander HeidenMG, CantleyLC, ThompsonCB. Understanding the warburg effect: the metabolic requirements of cell proliferation. Science 2009;324:1029-33.
4. AlmuhaidebA, PapathanasiouN, BomanjiJ. 18F-FDG PET/CT imaging in oncology. Ann Saudi Med 2011;31:3-13.
5. BarthelA, OkinoST, LiaoJ, NakataniK, LiJ, WhitlockJPJr, RothRA. Regulation of GLUT1 gene transcription by the serine/threonine kinase Akt1. J Biol Chem 1999;274:20281-6.
6. WiemanHL, WoffordJA, RathmellJC. Cytokine stimulation promotes glucose uptake via phosphatidylinositol-3 kinase/Akt regulation of Glut1 activity and trafficking. Mol Biol Cell 2007;18:1437-46.
7. DeprezJ, VertommenD, AlessiDR, HueL, RiderMH. Phosphorylation and activation of heart 6-phosphofructo-2-kinase by protein kinase B and other protein kinases of the insulin signaling cascades. J Biol Chem 1997;272:17269-75.
8. GottlobK, MajewskiN, KennedyS, KandelE, RobeyRB, HayN. Inhibition of early apoptotic events by Akt/PKB is dependent on the first committed step of glycolysis and mitochondrial hexokinase. Genes Dev 2001;15:1406-18.
9. LeeJH, LiuR, LiJ, ZhangC, WangY, CaiQ, QianX, XiaY, ZhengY, PiaoY, ChenQ, de GrootJF, JiangT, LuZ. Stabilization of phosphofructokinase 1 platelet isoform by AKT promotes tumorigenesis. Nat Commun 2017;8:949.
10. MurakamiT, NishiyamaT, ShirotaniT, ShinoharaY, KanM, IshiiK, KanaiF, NakazuruS, EbinaY. Identification of two enhancer elements in the gene encoding the type 1 glucose transporter from the mouse which are responsive to serum, growth factor, and oncogenes. J Biol Chem 1992;267:9300-6.
11. EagleH. The minimum vitamin requirements of the L and HeLa cells in tissue culture, the production of specific vitamin deficiencies, and their cure. J Exp Med 1955;102:595-600.
12. NicklinP, BergmanP, ZhangB, TriantafellowE, WangH, NyfelerB, YangH, HildM, KungC, WilsonC, MyerVE, MacKeiganJP, PorterJA, WangYK, CantleyLC, FinanPM, MurphyLO. Bidirectional transport of amino acids regulates mTOR and autophagy. Cell 2009;136:521-34.
13. KairaK, OriuchiN, ImaiH, ShimizuK, YanagitaniN, SunagaN, HisadaT, TanakaS, IshizukaT, KanaiY, EndouH, NakajimaT, MoriM. Prognostic significance of L-type amino acid transporter 1 expression in resectable stage I-III nonsmall cell lung cancer. Br J Cancer 2008;98:742-8.
14. SakataT, FerdousG, TsurutaT, SatohT, BabaS, MutoT, UenoA, KanaiY, EndouH, OkayasuI. L-type amino-acid transporter 1 as a novel biomarker for high-grade malignancy in prostate cancer. Pathol Int 2009;59:7-18.
15. LiebermanBP, PloesslK, WangL, QuW, ZhaZ, WiseDR, ChodoshLA, BelkaG, ThompsonCB, KungHF. PET imaging of glutaminolysis in tumors by 18F-(2S,4R)4-fluoroglutamine. J Nucl Med 2011;52:1947-55.
16. VennetiS, DunphyMP, ZhangH, PitterKL, ZanzonicoP, CamposC, CarlinSD, La RoccaG, LyashchenkoS, PloesslK, RohleD, OmuroAM, CrossJR, BrennanCW, WeberWA, HollandEC, MellinghoffIK, KungHF, LewisJS, ThompsonCB. Glutamine-based PET imaging facilitates enhanced metabolic evaluation of gliomas in vivo. Sci Transl Med 2015;7:274ra17.
17. WangR, DillonCP, ShiLZ, MilastaS, CarterR, FinkelsteinD, McCormickLL, FitzgeraldP, ChiH, MungerJ, GreenDR. The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation. Immunity 2011;35:871-82.
18. WiseDR, DeBerardinisRJ, MancusoA, SayedN, ZhangXY, PfeifferHK, NissimI, DaikhinE, YudkoffM, McMahonSB, ThompsonCB. Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction. Proc Natl Acad Sci 2008;105:18782-7.
19. EberhardySR, FarnhamPJ. c-Myc mediates activation of the cad promoter via a post-RNA polymerase II recruitment mechanism. J Biol Chem 2001;276:48562-71.
20. GaoP, TchernyshyovI, ChangTC, LeeYS, KitaK, OchiT, ZellerKI, De MarzoAM, Van EykJE, MendellJT, DangCV. c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism. Nature 2009;458:762-5.
21. MannavaS, GrachtchoukV, WheelerLJ, ImM, ZhuangD, SlavinaEG, MathewsCK, ShewachDS, NikiforovMA. Direct role of nucleotide metabolism in C-MYC-dependent proliferation of melanoma cells. Cell Cycle 2008;7:2392-400.
22. ReynoldsMR, LaneAN, RobertsonB, KempS, LiuY, HillBG, DeanDC, ClemBF. Control of glutamine metabolism by the tumor suppressor Rb. Oncogene 2014;33:556-66.
23. KuoW, LinJ, TangTK. Human glucose-6-phosphate dehydrogenase (G6PD) gene transforms NIH 3T3 cells and induces tumors in nude mice. Int J cancer 2000;85:857-64.
24. WangC, GuoK, GaoD, KangX, JiangK, LiY, SunL, ZhangS, SunC, LiuX, WuW, YangP, LiuY. Identification of transaldolase as a novel serum biomarker for hepatocellular carcinoma metastasis using xenografted mouse model and clinic samples. Cancer Lett 2011;313:154-66.
25. LocasaleJW, GrassianAR, MelmanT, LyssiotisCA, MattainiKR, BassAJ, HeffronG, MetalloCM, MuranenT, SharfiH, SasakiAT, AnastasiouD, MullarkyE, VokesNI, SasakiM, BeroukhimR, StephanopoulosG, LigonAH, MeyersonM, RichardsonAL, ChinL, WagnerG, AsaraJM, BruggeJS, CantleyLC, Vander HeidenMG. Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis. Nat Genet 2011;43:869-74.
26. PossematoR, MarksKM, ShaulYD, PacoldME, KimD, BirsoyK, SethumadhavanS, WooHK, JangHG, JhaAK, ChenWW, BarrettFG, StranskyN, TsunZY, CowleyGS, BarretinaJ, KalaanyNY, HsuPP, OttinaK, ChanAM, YuanB, GarrawayLA, RootDE, Mino-KenudsonM, BrachtelEF, DriggersEM, SabatiniDM. Functional genomics reveal that the serine synthesis pathway is essential in breast cancer. Nature 2011;476:346-50.
27. BauerDE, HatzivassiliouG, ZhaoF, AndreadisC, ThompsonCB. ATP citrate lyase is an important component of cell growth and transformation. Oncogene 2005;24:6314-22.
28. HatzivassiliouG, ZhaoF, BauerDE, AndreadisC, ShawAN, DhanakD, HingoraniSR, TuvesonDA, ThompsonCB. ATP citrate lyase inhibition can suppress tumor cell growth. Cancer Cell 2005;8:311-21.
29. BerwickDC, HersI, HeesomKJ, MouleSK, TavareJM. The identification of ATP-citrate lyase as a protein kinase B (Akt) substrate in primary adipocytes. J Biol Chem 2002;277:33895-900.
30. BirsoyK, WangT, ChenWW, FreinkmanE, Abu-RemailehM, SabatiniDM. An essential role of the mitochondrial electron transport chain in cell proliferation is to enable aspartate synthesis. Cell 2015;162:540-51.
31. SullivanLB, GuiDY, HosiosAM, BushLN, FreinkmanE, Vander HeidenMG. Supporting aspartate biosynthesis is an essential function of respiration in proliferating cells. Cell 2015;162:552-63.
32. DeBerardinisRJ, MancusoA, DaikhinE, NissimI, YudkoffM, WehrliS, ThompsonCB. Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proc Natl Acad Sci U S A 2007;104:19345-50.
33. YunevaM, ZamboniN, OefnerP, SachidanandamR, LazebnikY. Deficiency in glutamine but not glucose induces MYC-dependent apoptosis in human cells. J Cell Biol 2007;178:93-105.
34. MetalloCM, GameiroPA, BellEL, MattainiKR, YangJ, HillerK, JewellCM, JohnsonZR, IrvineDJ, GuarenteL, KelleherJK, Vander HeidenMG, IliopoulosO, StephanopoulosG. Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia. Nature 2011;481:380-4.
35. BrosnanJT. Interorgan amino acid transport and its regulation. J Nutr 2003;133:2068S-72S.
36. WangJB, EricksonJW, FujiR, RamachandranS, GaoP, DinavahiR, WilsonKF, AmbrosioAL, DiasSM, DangCV, CerioneRA. Targeting mitochondrial glutaminase activity inhibits oncogenic transformation. Cancer Cell 2010;18:207-19.
37. KrebsHA. Metabolism of amino-acids: the synthesis of glutamine from glutamic acid and ammonia, and the enzymic hydrolysis of glutamine in animal tissues. Biochem J 1935;29:1951-69.
38. YieldingKL, TomkinsGM. An effect of L-leucine and other essential amino acids on the structure and activity of glutamic dehydrogenase. Proc Natl Acad Sci U S A 1961;47:983-9.
39. LongJ, LangZW, WangHG, WangTL, WangBE, LiuSQ. Glutamine synthetase as an early marker for hepatocellular carcinoma based on proteomic analysis of resected small hepatocellular carcinomas. Hepatobiliary Pancreat Dis Int 2010;9:296-305.
40. RosatiA, PolianiPL, TodeschiniA, CominelliM, MedicinaD, CenzatoM, SimonciniEL, MagriniSM, BuglioneM, GrisantiS, PadovaniA. Glutamine synthetase expression as a valuable marker of epilepsy and longer survival in newly diagnosed glioblastoma multiforme. Neuro Oncol 2013;15:618-25.
41. GameiroPA, YangJ, MeteloAM, Pérez-CarroR, BakerR, WangZ, ArreolaA, RathmellWK, OlumiA, López-LarrubiaP, StephanopoulosG, IliopoulosO. In vivo HIF-mediated reductive carboxylation is regulated by citrate levels and sensitizes VHL-deficient cells to glutamine deprivation. Cell Metab 2013;17:372-85.
42. JiangL, ShestovAA, SwainP, YangC, ParkerSJ, WangQA, TeradaLS, AdamsND, McCabeMT, PietrakB, SchmidtS, MetalloCM, DrankaBP, SchwartzB, DeBerardinisRJ. Reductive carboxylation supports redox homeostasis during anchorage-independent growth. Nature 2016;532:255-8.
43. MullenAR, WheatonWW, JinES, ChenPH, SullivanLB, ChengT, YangY, LinehanWM, ChandelNS, DeBerardinisRJ. Reductive carboxylation supports growth in tumour cells with defective mitochondria. Nature 2011;481:385-8.
44. PatelD, MenonD, BernfeldE, MrozV, KalanS, LoayzaD, FosterDA. Aspartate rescues S-phase arrest caused by suppression of glutamine utilization in KRas-driven cancer cells. J Biol Chem 2016;291:9322-9.
45. ZhangJ, FanJ, VennetiS, CrossJR, TakagiT, BhinderB, DjaballahH, KanaiM, ChengEH, JudkinsAR, PawelB, BaggsJ, CherryS, RabinowitzJD, ThompsonCB. Asparagine plays a critical role in regulating cellular adaptation to glutamine depletion. Mol Cell 2014;56:205-18.
46. HaoY, SamuelsY, LiQ, KrokowskiD, GuanBJ, WangC, JinZ, DongB, CaoB, FengX, XiangM, XuC, FinkS, MeropolNJ, XuY, ConlonRA, MarkowitzS, KinzlerKW, VelculescuVE, BrunengraberH, WillisJE, LaFramboiseT, HatzoglouM, ZhangGF, VogelsteinB, WangZ. Oncogenic PIK3CA mutations reprogram glutamine metabolism in colorectal cancer. Nat Commun 2016;7:11971.
47. XuP, OosterveerMH, SteinS, DemagnyH, RyuD, MoullanN, WangX, CanE, ZamboniN, CommentA, AuwerxJ, SchoonjansK. LRH-1-dependent programming of mitochondrial glutamine processing drives liver cancer. Genes Dev 2016;30:1255-60.
48. ViéN, CopoisV, Bascoul-MolleviC, DenisV, BecN, RobertB, FraslonC, ConseillerE, MolinaF, LarroqueC, MartineauP, Del RioM, GongoraC. Overexpression of phosphoserine aminotransferase PSAT1 stimulates cell growth and increases chemoresistance of colon cancer cells. Mol Cancer 2008;7:14.
49. LiuW, LeA, HancockC, LaneAN, DangCV, FanTW, PhangJM. Reprogramming of proline and glutamine metabolism contributes to the proliferative and metabolic responses regulated by oncogenic transcription factor c-MYC. Proc Natl Acad Sci U S A 2012;109:8983-8.
50. LiH, MeiningerCJ, BazerFW, WuG. Intracellular sources of ornithine for polyamine synthesis in endothelial cells. Amino Acids 2016;48:2401-10.
51. AltmanBJ, StineZE, DangCV. From Krebs to clinic: glutamine metabolism to cancer therapy. Nat Rev Cancer 2016;16:619-34.
52. HosiosAM, HechtVC, DanaiLV, JohnsonMO, RathmellJC, SteinhauserML, ManalisSR, Vander HeidenMG. Amino acids rather than glucose account for the majority of cell mass in proliferating mammalian cells. Dev Cell 2016;36:540-9.
53. XiangL, XieG, LiuC, ZhouJ, ChenJ, YuS, LiJ, PangX, ShiH, LiangH. Knock-down of glutaminase 2 expression decreases glutathione, NADH, and sensitizes cervical cancer to ionizing radiation. Biochim Biophys Acta 2013;1833:2996-3005.
54. TimmermanLA, HoltonT, YunevaM, LouieRJ, PadróM, DaemenA, HuM, ChanDA, EthierSP, van't VeerLJ, PolyakK, McCormickF, GrayJW. Glutamine sensitivity analysis identifies the xCT antiporter as a common triple-negative breast tumor therapeutic target. Cancer Cell 2013;24:450-65.
55. TsuchihashiK, OkazakiS, OhmuraM, IshikawaM, SampetreanO, OnishiN, WakimotoH, YoshikawaM, SeishimaR, IwasakiY, MorikawaT, AbeS, TakaoA, ShimizuM, MasukoT, NaganeM, FurnariFB, AkiyamaT, SuematsuM, BabaE, AkashiK, SayaH, NaganoO. The EGF receptor promotes the malignant potential of glioma by regulating amino acid transport system xc(-). Cancer Res 2016;76:2954-63.
56. KoppulaP, ZhangY, ShiJ, LiW, GanB. The glutamate/cystine antiporter SLC7A11/xCT enhances cancer cell dependency on glucose by exporting glutamate. J Biol Chem 2017;292:14240-9.
57. SayinVI, LeBoeufSE, SinghSX, DavidsonSM, BiancurD, GuzelhanBS, AlvarezSW, WuWL, KarakousiTR, ZavitsanouAM, UbriacoJ, MuirA, KaragiannisD, MorrisPJ, ThomasCJ, PossematoR, Vander HeidenMG, PapagiannakopoulosT. Activation of the NRF2 antioxidant program generates an imbalance in central carbon metabolism in cancer. Elife 2017; doi: 10.7554/eLife.28083.
58. ShinCS, MishraP, WatrousJD, CarelliV, D'AurelioM, JainM, ChanDC. The glutamate/cystine xCT antiporter antagonizes glutamine metabolism and reduces nutrient flexibility. Nat Commun 2017;8:15074.
59. SonJ, LyssiotisCA, YingH, WangX, HuaS, LigorioM, PereraRM, FerroneCR, MullarkyE, Shyh-ChangN, KangY, FlemingJB, BardeesyN, AsaraJM, HaigisMC, DePinhoRA, CantleyLC, KimmelmanAC. Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway. Nature 2013;496:101-5.
60. FigueroaME, Abdel-WahabO, LuC, WardPS, PatelJ, ShihA, LiY, BhagwatN, VasanthakumarA, FernandezHF, TallmanMS, SunZ, WolniakK, PeetersJK, LiuW, ChoeSE, FantinVR, PaiettaE, LöwenbergB, LichtJD, GodleyLA, DelwelR, ValkPJ, ThompsonCB, LevineRL, MelnickA. Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell 2010;18:553-67.
61. WardPS, PatelJ, WiseDR, Abdel-WahabO, BennettBD, CollerHA, CrossJR, FantinVR, HedvatCV, PerlAE, RabinowitzJD, CarrollM, SuSM, SharpKA, LevineRL, ThompsonCB. The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate. Cancer Cell 2010;17:225-34.
62. LetouzéE, MartinelliC, LoriotC, BurnichonN, AbermilN, OttolenghiC, JaninM, MenaraM, NguyenAT, BenitP, BuffetA, MarcaillouC, BertheratJ, AmarL, RustinP, De ReynièsA, Gimenez-RoqueploAP, FavierJ. SDH mutations establish a hypermethylator phenotype in paraganglioma. Cancer Cell 2013;23:739-52.
63. XiaoM, YangH, XuW, MaS, LinH, ZhuH, LiuL, LiuY, YangC, XuY, ZhaoS, YeD, XiongY, GuanKL. Inhibition of a-KG-dependent histone and DNA demethylases by fumarate and succinate that are accumulated in mutations of FH and SDH tumor suppressors. Genes Dev 2012;26:1326-38.
64. PanM, ReidMA, LowmanXH, KulkarniRP, TranTQ, LiuX, YangY, Hernandez-DaviesJE, RosalesKK, LiH, HugoW, SongC, XuX, SchonesDE, AnnDK, GradinaruV, LoRS, LocasaleJW, KongM. Regional glutamine deficiency in tumours promotes dedifferentiation through inhibition of histone demethylation. Nat Cell Biol 2016;18:1090-101.
65. van GeldermalsenM, WangQ, NagarajahR, MarshallAD, ThoengA, GaoD, RitchieW, FengY, BaileyCG, DengN, HarveyK, BeithJM, SelingerCI, O'TooleSA, RaskoJE, HolstJ. ASCT2/SLC1A5 controls glutamine uptake and tumour growth in triple-negative basal-like breast cancer. Oncogene 2016;35:3201-8.
66. BröerA, RahimiF, BröerS. Deletion of amino acid transporter ASCT2 (SLC1A5) reveals an essential role for transporters SNAT1 (SLC38A1) and SNAT2 (SLC38A2) to sustain glutaminolysis in cancer cells. J Biol Chem 2016;291:13194-205.
67. PollettaL, VernucciE, CarnevaleI, ArcangeliT, RotiliD, PalmerioS, SteegbornC, NowakT, SchutkowskiM, PellegriniL, SansoneL, VillanovaL, RunciA, PucciB, MorganteE, FiniM, MaiA, RussoMA, TafaniM. SIRT5 regulation of ammonia-induced autophagy and mitophagy. Autophagy 2015;11:253-70.
68. MasamhaCP, XiaZ, YangJ, AlbrechtTR, LiM, ShyuAB, LiW, WagnerEJ. CFIm25 links alternative polyadenylation to glioblastoma tumour suppression. Nature 2014;510:412-6.
69. RedisRS, VelaLE, LuW, Ferreira de OliveiraJ, IvanC, Rodriguez-AguayoC, AdamoskiD, PasculliB, TaguchiA, ChenY, FernandezAF, ValledorL, Van RoosbroeckK, ChangS, ShahM, KinnebrewG, HanL, AtlasiY, CheungLH, HuangGY, MonroigP, RamirezMS, Catela IvkovicT, VanL, LingH, GafàR, KapitanovicS, LanzaG, BanksonJA, HuangP, LaiSY, BastRC, RosenblumMG, RadovichM, IvanM, BartholomeuszG, LiangH, FragaMF, WidgerWR, HanashS, Berindan-NeagoeI, Lopez-BeresteinG, AmbrosioALB, Gomes DiasSM, CalinGA. Allele-specific reprogramming of cancer metabolism by the long non-coding RNA CCAT2. Mol Cell 2016;61:520-34.
70. ColomboSL, Palacios-CallenderM, FrakichN, CarcamoS, KovacsI, TudzarovaS, MoncadaS. Molecular basis for the differential use of glucose and glutamine in cell proliferation as revealed by synchronized HeLa cells. Proc Natl Acad Sci U S A 2011;108:21069-74.
71. FahienLA, KmiotekE. Regulation of glutamate dehydrogenase by palmitoyl-coenzyme A. Arch Biochem Biophys 1981;212:247-53.
72. FriedenC. Glutamate dehydrogenase. V. The relation of enzyme structure to the catalytic function. J Biol Chem 1963;238:3286-99.
73. TomitaT, KuzuyamaT, NishiyamaM. Structural basis for leucine-induced allosteric activation of glutamate dehydrogenase. J Biol Chem 2011;286:37406-13.
74. HaigisMC, MostoslavskyR, HaigisKM, FahieK, ChristodoulouDC, MurphyAJ, ValenzuelaDM, YancopoulosGD, KarowM, BlanderG, WolbergerC, ProllaTA, WeindruchR, AltFW, GuarenteL. SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells. Cell 2006;126:941-54.
75. WangY, FanS, LuJ, ZhangZ, WuD, WuZ, ZhengY. GLUL promotes cell proliferation in breast cancer. J Cell Biochem 2017;118:2018-25.
76. van der VosKE, EliassonP, Proikas-CezanneT, VervoortSJ, van BoxtelR, PutkerM, van ZutphenIJ, MautheM, ZellmerS, PalsC, VerhagenLP, Groot KoerkampMJ, BraatAK, DansenTB, HolstegeFC, GebhardtR, BurgeringBM, CofferPJ. Modulation of glutamine metabolism by the PI(3)K-PKB-FOXO network regulates autophagy. Nat Cell Biol 2012;14:829-37.
77. BottAJ, PengIC, FanY, FaubertB, ZhaoL, LiJ, NeidlerS, SunY, JaberN, KrokowskiD, LuW, PanJA, PowersS, RabinowitzJ, HatzoglouM, MurphyDJ, JonesR, WuS, GirnunG, ZongWX. Oncogenic myc induces expression of glutamine synthetase through promoter demethylation. Cell Metab 2015;22:1068-77.
78. CoxAG, HwangKL, BrownKK, EvasonK, BeltzS, TsomidesA, O'ConnorK, GalliGG, YimlamaiD, ChhangawalaS, YuanM, LienEC, WucherpfennigJ, NissimS, MinamiA, CohenDE, CamargoFD, AsaraJM, HouvrasY, StainierDYR, GoesslingW. Yap reprograms glutamine metabolism to increase nucleotide biosynthesis and enable liver growth. Nat Cell Biol 2016;18:886-96.
79. AradG, FreikopfA, KulkaRG. Glutamine-stimulated modification and degradation of glutamine synthetase in hepatoma tissue culture cells. Cell 1976;8:95-101.
80. DemarsR. The inhibition by glutamine of glutamyl transferase formation in cultures of human cells. Biochim Biophys Acta 1958;27:435-6.
81. NguyenTV, LeeJE, SweredoskiMJ, YangSJ, JeonSJ, HarrisonJS, YimJH, LeeSG, HandaH, KuhlmanB, JeongJS, ReitsmaJM, ParkCS, HessS, DeshaiesRJ. Glutamine triggers acetylation-dependent degradation of glutamine synthetase via the thalidomide receptor cereblon. Mol Cell 2016;61:809-20.
82. Abu AboudO, HabibSL, TrottJ, StewartB, LiangS, ChaudhariAJ, SutcliffeJ, WeissRH. Glutamine addiction in kidney cancer suppresses oxidative stress and can be exploited for real-time imaging. Cancer Res 2017;77:6746-58.
83. PetroniniPG, UrbaniS, AlfieriR, BorghettiAF, GuidottiGG. Cell susceptibility to apoptosis by glutamine deprivation and rescue: survival and apoptotic death in cultured lymphoma-leukemia cell lines. J Cell Physiol 1996;169:175-85.
84. WeinbergF, HamanakaR, WheatonWW, WeinbergS, JosephJ, LopezM, KalyanaramanB, MutluGM, BudingerGR, ChandelNS. Mitochondrial metabolism and ROS generation are essential for Kras-mediated tumorigenicity. Proc Natl Acad Sci U S A 2010;107:8788-93.
85. TarditoS, OudinA, AhmedSU, FackF, KeunenO, ZhengL, MileticH, SakariassenPØ, WeinstockA, WagnerA, LindsaySL, HockAK, BarnettSC, RuppinE, MørkveSH, Lund-JohansenM, ChalmersAJ, BjerkvigR, NiclouSP, GottliebE. Glutamine synthetase activity fuels nucleotide biosynthesis and supports growth of glutamine-restricted glioblastoma. Nat Cell Biol 2015;17:1556-68.
86. PavlovaNN, HuiS, GhergurovichJM, FanJ, IntlekoferAM, WhiteRM, RabinowitzJD, ThompsonCB, ZhangJ. As extracellular glutamine levels decline, asparagine becomes an essential amino acid. Cell Metab 2018;27:428-38.
87. KrallAS, XuS, GraeberTG, BraasD, ChristofkHR. Asparagine promotes cancer cell proliferation through use as an amino acid exchange factor. Nat Commun 2016;7:11457.
88. DuránRV, OppligerW, RobitailleAM, HeiserichL, SkendajR, GottliebE, HallMN. Glutaminolysis activates Rag-mTORC1 signaling. Mol Cell 2012;47:349-58.
89. DuránRV, MacKenzieED, BoulahbelH, FrezzaC, HeiserichL, TarditoS, BussolatiO, RochaS, HallMN, GottliebE. HIF-independent role of prolyl hydroxylases in the cellular response to amino acids. Oncogene 2013;32:4549-56.
90. JewellJL, KimYC, RussellRC, YuFX, ParkHW, PlouffeSW, TagliabracciVS, GuanKL. Metabolism. Differential regulation of mTORC1 by leucine and glutamine. Science 2015;347:194-8.
91. TanHWS, SimAYL, LongYC. Glutamine metabolism regulates autophagy-dependent mTORC1 reactivation during amino acid starvation. Nat Commun 2017;8:338.
92. VillarVH, NguyenTL, DelcroixV, TerésS, BouchecareilhM, SalinB, BodineauC, VacherP, PriaultM, SoubeyranP, DuránRV. mTORC1 inhibition in cancer cells protects from glutaminolysis-mediated apoptosis during nutrient limitation. Nat Commun 2017;8:14124.
93. CsibiA, FendtSM, LiC, PoulogiannisG, ChooAY, ChapskiDJ, JeongSM, DempseyJM, ParkhitkoA, MorrisonT, HenskeEP, HaigisMC, CantleyLC, StephanopoulosG, YuJ, BlenisJ. The mTORC1 pathway stimulates glutamine metabolism and cell proliferation by repressing SIRT4. Cell 2013;153:840-54.
94. JeongSM, XiaoC, FinleyLW, LahusenT, SouzaAL, PierceK, LiYH, WangX, LaurentG, GermanNJ, XuX, LiC, WangRH, LeeJ, CsibiA, CerioneR, BlenisJ, ClishCB, KimmelmanA, DengCX, HaigisMC. SIRT4 has tumor-suppressive activity and regulates the cellular metabolic response to DNA damage by inhibiting mitochondrial glutamine metabolism. Cancer Cell 2013;23:450-63.
95. CsibiA, LeeG, YoonSO, TongH, IlterD, EliaI, FendtSM, RobertsTM, BlenisJ. The mTORC1/S6K1 pathway regulates glutamine metabolism through the eIF4B-dependent control of c-Myc translation. Curr Biol 2014;24:2274-80.
96. ColoffJL, MurphyJP, BraunCR, HarrisIS, SheltonLM, KamiK, GygiSP, SelforsLM, BruggeJS. Differential glutamate metabolism in proliferating and quiescent mammary epithelial cells. Cell Metab 2016;23:867-80.
97. WhiteMA, LinC, RajapaksheK, DongJ, ShiY, TsoukoE, MukhopadhyayR, JassoD, DawoodW, CoarfaC, FrigoDE. Glutamine transporters are targets of multiple oncogenic signaling pathways in prostate cancer. Mol Cancer Res 2017;15:1017-28.
98. ScaliseM, PochiniL, GalluccioM, IndiveriC. Glutamine transport. From energy supply to sensing and beyond. Biochim Biophys Acta 2016;1857:1147-57.
99. TanakaK, SasayamaT, IrinoY, TakataK, NagashimaH, SatohN, KyotaniK, MizowakiT, ImahoriT, EjimaY, MasuiK, GiniB, YangH, HosodaK, SasakiR, MischelPS, KohmuraE. Compensatory glutamine metabolism promotes glioblastoma resistance to mTOR inhibitor treatment. J Clin Invest 2015;125:1591-602.
100. RobinsonMM, McBryantSJ, TsukamotoT, RojasC, FerrarisDV, HamiltonSK, HansenJC, CurthoysNP. Novel mechanism of inhibition of rat kidney-type glutaminase by bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide (BPTES). Biochem J 2007;406:407-14.
101. GrossMI, DemoSD, DennisonJB, ChenL, Chernov-RoganT, GoyalB, JanesJR, LaidigGJ, LewisER, LiJ, MackinnonAL, ParlatiF, RodriguezML, ShwonekPJ, SjogrenEB, StantonTF, WangT, YangJ, ZhaoF, BennettMK. Antitumor activity of the glutaminase inhibitor CB-839 in triple-negative breast cancer. Mol Cancer Ther 2014;13:890-901.
102. JacqueN, RonchettiAM, LarrueC, MeunierG, BirsenR, WillemsL, SalandE, DecroocqJ, MacielTT, LambertM, PoulainL, HospitalMA, SujobertP, JosephL, ChapuisN, LacombeC, MouraIC, DemoS, SarryJE, RecherC, MayeuxP, TamburiniJ, BouscaryD. Targeting glutaminolysis has antileukemic activity in acute myeloid leukemia and synergizes with BCL-2 inhibition. Blood 2015;126:1346-56.
103. KorangathP, TeoWW, SadikH, HanL, MoriN, HuijtsCM, WildesF, BhartiS, ZhangZ, Santa-MariaCA, TsaiH, DangCV, StearnsV, BhujwallaZM, SukumarS. Targeting glutamine metabolism in breast cancer with aminooxyacetate. Clin Cancer Res 2015;21:3263-73.
104. LiM, AllenA, SmithTJ. High throughput screening reveals several new classes of glutamate dehydrogenase inhibitors. Biochemistry 2007;46:15089-102.
105. QingG, LiB, VuA, SkuliN, WaltonZE, LiuX, MayesPA, WiseDR, ThompsonCB, MarisJM, HogartyMD, SimonMC. ATF4 regulates MYC-mediated neuroblastoma cell death upon glutamine deprivation. Cancer Cell 2012;22:631-44.
106. ChengT, SudderthJ, YangC, MullenAR, JinES, MatésJM, DeBerardinisRJ. Pyruvate carboxylase is required for glutamine-independent growth of tumor cells. Proc Natl Acad Sci U S A 2011;108:8674-9.
107. ChristenS, LorendeauD, SchmiederR, BroekaertD, MetzgerK, VeysK, EliaI, BuescherJM, OrthMF, DavidsonSM, GrünewaldTG, De BockK, FendtSM. Breast cancer-derived lung metastases show increased pyruvate carboxylase-dependent anaplerosis. Cell Rep 2016;17:837-48.
108. LinaresJF, CordesT, DuranA, Reina-CamposM, ValenciaT, AhnCS, CastillaEA, MoscatJ, MetalloCM, Diaz-MecoMT. ATF4-induced metabolic reprograming is a synthetic vulnerability of the p62-deficient tumor stroma. Cell Metab 2017;26:817-29.