Glutamine: Pleiotropic roles in tumor growth and stress resistance

Journal of Molecular Medicine

Volumn 89, Issue 3, 2011, Pages 229-236

  Shanware, Naval P ^a   Mullen, Andrew R ^b   DeBerardinis, Ralph J ^b   Abraham, Robert T ^a  

^a PFIZER INC   (United States)

^b UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

Author keywords

Cancer; Oncogenesis; Oxidative stress

Indexed keywords

GLUTAMINE;

AUTOPHAGY; CELL INVASION; CELL SURVIVAL; CELLULAR STRESS RESPONSE; HUMAN; METASTASIS; NONHUMAN; OXIDATIVE STRESS; REVIEW; SIGNAL TRANSDUCTION; TUMOR GROWTH;

AUTOPHAGY; GLUTAMINE; MODELS, BIOLOGICAL; NEOPLASMS; OXIDATIVE STRESS;

EID: 79955764625     PISSN: 09462716     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00109-011-0731-9     Document Type: Review

References (43)

1. Levine AJ, Puzio-Kuter AM (2010) The control of the metabolic switch in cancers by oncogenes and tumor suppressor genes. Science 330:1340-1344
2. DeBerardinis RJ, Cheng T (2009) Q's next: The diverse functions of glutamine in metabolism, cell biology and cancer. Oncogene 29:313-324
3. Reitzer LJ, Wice BM, Kennell D (1979) Evidence that glutamine, not sugar, is the major energy source for cultured HeLa cells. J Biol Chem 254:2669-2676 (Pubitemid 9196102)
4. Brand K (1985) Glutamine and glucose metabolism during thymocyte proliferation. Pathways of glutamine and glutamate metabolism. Biochem J 228:353-361 (Pubitemid 15061125)
5. DeBerardinis RJ, Mancuso A, Daikhin E, Nissim I, Yudkoff M, Wehrli S, Thompson CB (2007) Beyond aerobic glycolysis: Transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proc Natl Acad Sci USA 104:19345-19350
6. Lemons JM, Feng XJ, Bennett BD, Legesse-Miller A, Johnson EL, Raitman I, Pollina EA, Rabitz HA, Rabinowitz JD, Coller HA (2010) Quiescent fibroblasts exhibit high metabolic activity. PLoS Biol 8:e1000514. doi:10.1371/journal.pbio. 1000514
7. Yang C, Sudderth J, Dang T, Bachoo RG, McDonald JG, DeBerardinis RJ (2009) Glioblastoma cells require glutamate dehydrogenase to survive impairments of glucose metabolism or Akt signaling. Cancer Res 69:7986-7993
8. Choo AY, Kim SG, Vander Heiden MG, Mahoney SJ, Vu H, Yoon SO, Cantley LC, Blenis J (2010) Glucose addiction of TSC null cells is caused by failed mTORC1-dependent balancing of metabolic demand with supply. Mol Cell 38:487-499
9. Eng CH, Abraham RT (2010) Glutaminolysis yields a metabolic by-product that stimulates autophagy. Autophagy 6:968-970
10. Weinberg F, Hamanaka R, Wheaton WW, Weinberg S, Joseph J, Lopez M, Kalyanaraman B, Mutlu GM, Budinger GR, Chandel NS (2010) Mitochondrial metabolism and ROS generation are essential for Kras-mediated tumorigenicity. Proc Natl Acad Sci USA 107:8788-8793
11. Wellen KE, Thompson CB (2010) Cellular metabolic stress: Considering how cells respond to nutrient excess. Mol Cell 40:323-332
12. Gao P, Tchernyshyov I, Chang TC, Lee YS, Kita K, Ochi T, Zeller KI, De Marzo AM, Van Eyk JE, Mendell JT, Dang CV (2009) c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism. Nature 458:762-765
13. Yuneva M, Zamboni N, Oefner P, Sachidanandam R, Lazebnik Y (2007) Deficiency in glutamine but not glucose induces MYCdependent apoptosis in human cells. J Cell Biol 178:93-105 (Pubitemid 47026405)
14. Lora J, Alonso FJ, Segura JA, Lobo C, Marquez J, Mates JM (2004) Antisense glutaminase inhibition decreases glutathione antioxidant capacity and increases apoptosis in Ehrlich ascitic tumour cells. Eur J Biochem 271:4298-4306 (Pubitemid 39506759)
15. Benassi B, Fanciulli M, Fiorentino F, Porrello A, Chiorino G, Loda M, Zupi G, Biroccio A (2006) c-Myc phosphorylation is required for cellular response to oxidative stress. Mol Cell 21:509-519 (Pubitemid 43228006)
16. Wise DR, DeBerardinis RJ, Mancuso A, Sayed N, Zhang XY, Pfeiffer HK, Nissim I, Daikhin E, Yudkoff M, McMahon SB, Thompson CB (2008) Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction. Proc Natl Acad Sci USA 105:18782-18787
17. Li F, Wang Y, Zeller KI, Potter JJ, Wonsey DR, O'Donnell KA, Kim JW, Yustein JT, Lee LA, Dang CV (2005) Myc stimulates nuclearly encoded mitochondrial genes and mitochondrial biogenesis. Mol Cell Biol 25:6225-6234 (Pubitemid 40946570)
18. Moiseeva O, Mallette FA, Mukhopadhyay UK, Moores A, Ferbeyre G (2006) DNA damage signaling and p53-dependent senescence after prolonged beta-interferon stimulation. Mol Biol Cell 17:1583-1592 (Pubitemid 44011578)
19. Mallette FA, Gaumont-Leclerc MF, Ferbeyre G (2007) The DNA damage signaling pathway is a critical mediator of oncogeneinduced senescence. Genes Dev 21:43-48 (Pubitemid 46089705)
20. Wang JB, Erickson JW, Fuji R, Ramachandran S, Gao P, Dinavahi R, Wilson KF, Ambrosio AL, Dias SM, Dang CV, Cerione RA (2010) Targeting mitochondrial glutaminase activity inhibits oncogenic transformation. Cancer Cell 18:207-219
21. Schafer ZT, Grassian AR, Song L, Jiang Z, Gerhart-Hines Z, Irie HY, Gao S, Puigserver P, Brugge JS (2009) Antioxidant and oncogene rescue of metabolic defects caused by loss of matrix attachment. Nature 461:109-113
22. Shelton LM, Huysentruyt LC, Seyfried TN (2010) Glutamine targeting inhibits systemic metastasis in the VM-M3 murine tumor model. Int J Cancer 127:2478-2485. doi:10.1002/ijc.25431
23. Hu W, Zhang C, Wu R, Sun Y, Levine A, Feng Z (2010) Glutaminase 2, a novel p53 target gene regulating energy metabolism and antioxidant function. Proc Natl Acad Sci U S A 107:7455-7460
24. Suzuki S, Tanaka T, Poyurovsky MV, Nagano H, Mayama T, Ohkubo S, Lokshin M, Hosokawa H, Nakayama T, Suzuki Y, Sugano S, Sato E, Nagao T, Yokote K, Tatsuno I, Prives C (2010) Phosphate-activated glutaminase (GLS2), a p53-inducible regulator of glutamine metabolism and reactive oxygen species. Proc Natl Acad Sci U S A 107:7461-7466
25. Mates JM, Segura JA, Campos-Sandoval JA, Lobo C, Alonso L, Alonso FJ, Marquez J (2009) Glutamine homeostasis and mitochondrial dynamics. Int J Biochem Cell Biol 41:2051-2061
26. Curthoys NP, Watford M (1995) Regulation of glutaminase activity and glutamine metabolism. Annu Rev Nutr 15:133-159. doi:10.1146/annurev.nu.15. 070195.001025
27. Mizushima N, Levine B, Cuervo AM, Klionsky DJ (2008) Autophagy fights disease through cellular self-digestion. Nature 451:1069-1075 (Pubitemid 351317450)
28. Gibbons JJ, Abraham RT, Yu K (2009) Mammalian target of rapamycin: Discovery of rapamycin reveals a signaling pathway important for normal and cancer cell growth. Semin Oncol 36 (Suppl 3):S3-S17
29. Jung CH, Ro SH, Cao J, Otto NM, Kim DH (2010) mTOR regulation of autophagy. FEBS Lett 584:1287-1295
30. Nicklin P, Bergman P, Zhang B, Triantafellow E, Wang H, Nyfeler B, Yang H, Hild M, Kung C, Wilson C, Myer VE, MacKeigan JP, Porter JA, Wang YK, Cantley LC, Finan PM, Murphy LO (2009) Bidirectional transport of amino acids regulates mTOR and autophagy. Cell 136:521-534
31. Fuchs BC, Finger RE, Onan MC, Bode BP (2007) ASCT2 silencing regulates mammalian target-of-rapamycin growth and survival signaling in human hepatoma cells. Am J Physiol Cell Physiol 293:C55-C63 (Pubitemid 47105038)
32. Eng CH, Yu K, Lucas J, White E, Abraham RT (2010) Ammonia derived from glutaminolysis is a diffusible regulator of autophagy. Sci Signal 3: Ra31
33. Yu K, Shi C, Toral-Barza L, Lucas J, Shor B, Kim JE, Zhang WG, Mahoney R, Gaydos C, Tardio L, Kim SK, Conant R, Curran K, Kaplan J, Verheijen J, Ayral-Kaloustian S, Mansour TS, Abraham RT, Zask A, Gibbons JJ (2010) Beyond rapalog therapy: Preclinical pharmacology and antitumor activity of WYE-125132, an ATP-competitive and specific inhibitor of mTORC1 and mTORC2. Cancer Res 70:621-631
34. Sakiyama T, Musch MW, Ropeleski MJ, Tsubouchi H, Chang EB (2009) Glutamine increases autophagy under Basal and stressed conditions in intestinal epithelial cells. Gastroenterology 136:924-932
35. Braissant O (2010) Current concepts in the pathogenesis of urea cycle disorders. Mol Genet Metab 100(Suppl 1):S3-S12
36. Wilkinson DJ, Smeeton NJ, Watt PW (2010) Ammonia metabolism, the brain and fatigue; revisiting the link. Prog Neurobiol 91:200-219
37. Butterworth RF (2002) Pathophysiology of hepatic encephalopathy: A new look at ammonia. Metab Brain Dis 17:221-227 (Pubitemid 36204752)
38. Sontheimer H (2008) A role for glutamate in growth and invasion of primary brain tumors. J Neurochem 105:287-295 (Pubitemid 351490026)
39. Gatenby RA, Gillies RJ (2004) Why do cancers have high aerobic glycolysis? Nat Rev Cancer 4:891-899 (Pubitemid 39472955)
40. Gatenby RA, Smallbone K, Maini PK, Rose F, Averill J, Nagle RB, Worrall L, Gillies RJ (2007) Cellular adaptations to hypoxia and acidosis during somatic evolution of breast cancer. Br J Cancer 97:646-653 (Pubitemid 47339892)
41. Moellering RE, Black KC, Krishnamurty C, Baggett BK, Stafford P, Rain M, Gatenby RA, Gillies RJ (2008) Acid treatment of melanoma cells selects for invasive phenotypes. Clin Exp Metastasis 25:411-425. doi:10.1007/s10585-008- 9145-7
42. Sonveaux P, Vegran F, Schroeder T, Wergin MC, Verrax J, Rabbani ZN, De Saedeleer CJ, Kennedy KM, Diepart C, Jordan BF, Kelley MJ, Gallez B, Wahl ML, Feron O, Dewhirst MW (2008) Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice. J Clin Invest 118:3930-3942
43. Palkova Z, Janderova B, Gabriel J, Zikanova B, Pospisek M, Forstova J (1997) Ammonia mediates communication between yeast colonies. Nature 390:532-536. doi:10.1038/37398 (Pubitemid 28013137)