MTORC1-Dependent Metabolic Reprogramming Underlies Escape from Glycolysis Addiction in Cancer Cells

Cancer Cell

Volumn 29, Issue 4, 2016, Pages 548-562

  Pusapati, Raju V ^a   Daemen, Anneleen ^a   Wilson, Catherine ^a   Sandoval, Wendy ^a   Gao, Min ^a   Haley, Benjamin ^a   Baudy, Andreas R ^a   Hatzivassiliou, Georgia ^a   Evangelista, Marie ^a   Settleman, Jeff ^a,b  

^a GENENTECH INC   (United States)

^b Calico Life Sciences LLC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE TRIPHOSPHATE; EVEROLIMUS; GLUCOSE; GLUCOSE 6 PHOSPHATE ISOMERASE; GLUTAMINE; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; PHENFORMIN; SHORT HAIRPIN RNA; CYTOKINE; DEOXYGLUCOSE; GLUTAMINASE; GPI PROTEIN, HUMAN; MECHANISTIC TARGET OF RAPAMYCIN COMPLEX 1; MULTIPROTEIN COMPLEX; RIBOSOMAL PROTEIN S6 KINASE, 70KD, POLYPEPTIDE 1; S6 KINASE; SMALL INTERFERING RNA; TARGET OF RAPAMYCIN KINASE; TUMOR PROTEIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BIOMASS PRODUCTION; CANCER CELL; CANCER GROWTH; CANCER INHIBITION; CITRIC ACID CYCLE; CONTROLLED STUDY; FEMALE; GLUCOSE TRANSPORT; GLYCOLYSIS; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; MOUSE; NONHUMAN; NUCLEAR REPROGRAMMING; OXIDATIVE PHOSPHORYLATION; PENTOSE PHOSPHATE CYCLE; PRIORITY JOURNAL; PROTEIN DEPLETION; SIGNAL TRANSDUCTION; ANIMAL; ANTAGONISTS AND INHIBITORS; BIOSYNTHESIS; CARCINOMA; DRUG EFFECTS; DRUG POTENTIATION; DRUG RESISTANCE; DRUG SCREENING; ENERGY METABOLISM; GENETICS; HEPG2 CELL LINE; METABOLISM; METABOLOMICS; MOLECULARLY TARGETED THERAPY; MULTIMODALITY CANCER THERAPY; NEOPLASMS; NUDE MOUSE; OVARY TUMOR; PATHOLOGY; PHYSIOLOGY; RNA INTERFERENCE; TUMOR CELL LINE; TUMOR STEM CELL ASSAY;

ADENOSINE TRIPHOSPHATE; ANIMALS; CARCINOMA; CELL LINE, TUMOR; CITRIC ACID CYCLE; COMBINED MODALITY THERAPY; CYTOKINES; DEOXYGLUCOSE; DRUG RESISTANCE, NEOPLASM; DRUG SYNERGISM; ENERGY METABOLISM; EVEROLIMUS; FEMALE; GLUCOSE-6-PHOSPHATE ISOMERASE; GLUTAMINASE; GLUTAMINE; GLYCOLYSIS; HEP G2 CELLS; HUMANS; METABOLOMICS; MICE; MICE, NUDE; MOLECULAR TARGETED THERAPY; MULTIPROTEIN COMPLEXES; NEOPLASM PROTEINS; NEOPLASMS; OVARIAN NEOPLASMS; PENTOSE PHOSPHATE PATHWAY; RIBOSOMAL PROTEIN S6 KINASES, 70-KDA; RNA INTERFERENCE; RNA, SMALL INTERFERING; TOR SERINE-THREONINE KINASES; TUMOR STEM CELL ASSAY; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84962670514     PISSN: 15356108     EISSN: 18783686     Source Type: Journal    
DOI: 10.1016/j.ccell.2016.02.018     Document Type: Article

References (33)

1. Ben-Sahra I., Howell J.J., Asara J.M., Manning B.D. Stimulation of de novo pyrimidine synthesis by growth signaling through mTOR and S6K1. Science 2013, 339:1323-1328.
2. Birsoy K., Wang T., Chen W.W., Freinkman E., Abu-Remaileh M., Sabatini D.M. An essential role of the mitochondrial electron transport chain in cell proliferation is to enable aspartate synthesis. Cell 2015, 162:540-551.
3. Corcoran R.B., Rothenberg S.M., Hata A.N., Faber A.C., Piris A., Nazarian R.M., Brown R.D., Godfrey J.T., Winokur D., Walsh J., et al. TORC1 suppression predicts responsiveness to RAF and MEK inhibition in BRAF-mutant melanoma. Sci. Transl Med. 2013, 5:196ra198.
4. DeBerardinis R.J., Mancuso A., Daikhin E., Nissim I., Yudkoff M., Wehrli S., Thompson C.B. Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proc. Natl. Acad. Sci. USA 2007, 104:19345-19350.
5. Dennis P.B., Jaeschke A., Saitoh M., Fowler B., Kozma S.C., Thomas G. Mammalian TOR: a homeostatic ATP sensor. Science 2001, 294:1102-1105.
6. Di Cosimo S., Ferretti G., Papaldo P., Carlini P., Fabi A., Cognetti F. Lonidamine: efficacy and safety in clinical trials for the treatment of solid tumors. Drugs Today (Barc) 2003, 39:157-174.
7. Dibble C.C., Manning B.D. Signal integration by mTORC1 coordinates nutrient input with biosynthetic output. Nat. Cell Biol. 2013, 15:555-564.
8. Dragovich P.S., Fauber B.P., Corson L.B., Ding C.Z., Eigenbrot C., Ge H., Giannetti A.M., Hunsaker T., Labadie S., Liu Y., et al. Identification of substituted 2-thio-6-oxo-1,6-dihydropyrimidines as inhibitors of human lactate dehydrogenase. Bioorg. Med. Chem. Lett. 2013, 23:3186-3194.
9. Durán R.V., Oppliger W., Robitaille A.M., Heiserich L., Skendaj R., Gottlieb E., Hall M.N. Glutaminolysis activates Rag-mTORC1 signaling. Mol. Cell 2012, 47:349-358.
10. Düvel K., Yecies J.L., Menon S., Raman P., Lipovsky A.I., Souza A.L., Triantafellow E., Ma Q., Gorski R., Cleaver S., et al. Activation of a metabolic gene regulatory network downstream of mTOR complex 1. Mol. Cell 2010, 39:171-183.
11. Fan J., Ye J., Kamphorst J.J., Shlomi T., Thompson C.B., Rabinowitz J.D. Quantitative flux analysis reveals folate-dependent NADPH production. Nature 2014, 510:298-302.
12. Hirono Y., Fushida S., Yonemura Y., Yamamoto H., Watanabe H., Raz A. Expression of autocrine motility factor receptor correlates with disease progression in human gastric cancer. Br. J. Cancer 1996, 74:2003-2007.
13. Landau B.R., Laszlo J., Stengle J., Burk D. Certain metabolic and pharmacologic effects in cancer patients given infusions of 2-deoxy-D-glucose. J. Natl. Cancer Inst. 1958, 21:485-494.
14. Laplante M., Sabatini D.M. mTOR signaling in growth control and disease. Cell 2012, 149:274-293.
15. Le A., Lane A.N., Hamaker M., Bose S., Gouw A., Barbi J., Tsukamoto T., Rojas C.J., Slusher B.S., Zhang H., et al. Glucose-independent glutamine metabolism via TCA cycling for proliferation and survival in B cells. Cell Metab. 2012, 15:110-121.
16. Locasale J.W., Grassian A.R., Melman T., Lyssiotis C.A., Mattaini K.R., Bass A.J., Heffron G., Metallo C.M., Muranen T., Sharfi H., et al. Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis. Nat. Genet. 2011, 43:869-874.
17. Maddocks O.D., Berkers C.R., Mason S.M., Zheng L., Blyth K., Gottlieb E., Vousden K.H. Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells. Nature 2013, 493:542-546.
18. Maschek G., Savaraj N., Priebe W., Braunschweiger P., Hamilton K., Tidmarsh G.F., De Young L.R., Lampidis T.J. 2-Deoxy-D-glucose increases the efficacy of adriamycin and paclitaxel in human osteosarcoma and non-small cell lung cancers in vivo. Cancer Res. 2004, 64:31-34.
19. Metcalfe C., Alicke B., Crow A., Lamoureux M., Dijkgraaf G.J., Peale F., Gould S.E., de Sauvage F.J. PTEN loss mitigates the response of medulloblastoma to Hedgehog pathway inhibition. Cancer Res. 2013, 73:7034-7042.
20. Morken T.S., Brekke E., Håberg A., Widerøe M., Brubakk A.M., Sonnewald U. Neuron-astrocyte interactions, pyruvate carboxylation and the pentose phosphate pathway in the neonatal rat brain. Neurochem. Res. 2014, 39:556-569.
21. Mullen A.R., Wheaton W.W., Jin E.S., Chen P.H., Sullivan L.B., Cheng T., Yang Y., Linehan W.M., Chandel N.S., DeBerardinis R.J. Reductive carboxylation supports growth in tumour cells with defective mitochondria. Nature 2012, 481:385-388.
22. Porstmann T., Santos C.R., Griffiths B., Cully M., Wu M., Leevers S., Griffiths J.R., Chung Y.L., Schulze A. SREBP activity is regulated by mTORC1 and contributes to Akt-dependent cell growth. Cell Metab. 2008, 8:224-236.
23. Possemato R., Marks K.M., Shaul Y.D., Pacold M.E., Kim D., Birsoy K., Sethumadhavan S., Woo H.K., Jang H.G., Jha A.K., et al. Functional genomics reveal that the serine synthesis pathway is essential in breast cancer. Nature 2011, 476:346-350.
24. Prasanna V.K., Venkataramana N.K., Dwarakanath B.S., Santhosh V. Differential responses of tumors and normal brain to the combined treatment of 2DG and radiation in glioablastoma. J. Cancer Res. Ther. 2009, 5(Suppl 1):S44-S47.
25. Rajagopalan K.N., Egnatchik R.A., Calvaruso M.A., Wasti A.T., Padanad M.S., Boroughs L.K., Ko B., Hensley C.T., Acar M., Hu Z., et al. Metabolic plasticity maintains proliferation in pyruvate dehydrogenase deficient cells. Cancer Metab. 2015, 3:7.
26. Robitaille A.M., Christen S., Shimobayashi M., Cornu M., Fava L.L., Moes S., Prescianotto-Baschong C., Sauer U., Jenoe P., Hall M.N. Quantitative phosphoproteomics reveal mTORC1 activates de novo pyrimidine synthesis. Science 2013, 339:1320-1323.
27. Son J., Lyssiotis C.A., Ying H., Wang X., Hua S., Ligorio M., Perera R.M., Ferrone C.R., Mullarky E., Shyh-Chang N., et al. Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway. Nature 2013, 496:101-105.
28. Sullivan L.B., Gui D.Y., Hosios A.M., Bush L.N., Freinkman E., Vander Heiden M.G. Supporting aspartate biosynthesis is an essential function of respiration in proliferating cells. Cell 2015, 162:552-563.
29. Vander Heiden M.G. Targeting cancer metabolism: a therapeutic window opens. Nat. Rev. Drug Discov. 2011, 10:671-684.
30. Warburg O. On the origin of cancer cells. Science 1956, 123:309-314.
31. Wellen K.E., Thompson C.B. A two-way street: reciprocal regulation of metabolism and signalling. Nat. Rev. Mol. Cell Biol. 2012, 13:270-276.
32. Wellen K.E., Lu C., Mancuso A., Lemons J.M., Ryczko M., Dennis J.W., Rabinowitz J.D., Coller H.A., Thompson C.B. The hexosamine biosynthetic pathway couples growth factor-induced glutamine uptake to glucose metabolism. Genes Dev. 2010, 24:2784-2799.
33. Yang C., Ko B., Hensley C.T., Jiang L., Wasti A.T., Kim J., Sudderth J., Calvaruso M.A., Lumata L., Mitsche M., et al. Glutamine oxidation maintains the TCA cycle and cell survival during impaired mitochondrial pyruvate transport. Mol. Cell 2014, 56:414-424.