Glucose-dependent anaplerosis in cancer cells is required for cellular redox balance in the absence of glutamine

Scientific Reports

Volumn 6, Issue , 2016, Pages

  Cetinbas, Naniye Malll ^a,b,d   Sudderth, Jessica ^c   Harris, Robert C ^c   Cebeci, Aysun ^d,e   Negri, Gian L ^a,b   Yllmaz, Ömer H ^d,f   Deberardinis, Ralph J ^c   Sorensen, Poul H ^a,b  

^a UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^b BRITISH COLUMBIA CANCER RESEARCH CENTRE   (Canada)

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

^d MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

^e ABDULLAH GUL UNIVERSITY   (Turkey)

^f MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIOXIDANT; GLUCOSE; GLUTAMINE; GLUTATHIONE; PYRUVIC ACID; REACTIVE OXYGEN METABOLITE;

APOPTOSIS; CELL SURVIVAL; CHEMISTRY; CITRIC ACID CYCLE; GENETICS; HUMAN; METABOLISM; NEOPLASM; OXIDATION REDUCTION REACTION; PATHOLOGY; TUMOR CELL LINE;

ANTIOXIDANTS; APOPTOSIS; CELL LINE, TUMOR; CELL SURVIVAL; CITRIC ACID CYCLE; GLUCOSE; GLUTAMINE; GLUTATHIONE; HUMANS; NEOPLASMS; OXIDATION-REDUCTION; PYRUVIC ACID; REACTIVE OXYGEN SPECIES;

EID: 84986592993     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/srep32606     Document Type: Article

References (51)

1. Cantor, J. R. & Sabatini, D. M. Cancer cell metabolism: one hallmark, many faces. Cancer Discov 2, 881-898 (2012).
2. DeBerardinis, R. J., Lum, J. J., Hatzivassiliou, G. & Thompson, C. B. The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab 7, 11-20 (2008).
3. Deberardinis, R. J., Sayed, N., Ditsworth, D. & Thompson, C. B. Brick by brick: metabolism and tumor cell growth. Curr Opin Genet Dev 18, 54-61 (2008).
4. Boroughs, L. K. & DeBerardinis, R. J. Metabolic pathways promoting cancer cell survival and growth. Nat Cell Biol 17, 351-359 (2015).
5. Eagle, H. Nutrition needs of mammalian cells in tissue culture. Science 122, 501-514 (1955).
6. DeBerardinis, R. J. & Cheng, T. Q's next: the diverse functions of glutamine in metabolism, cell biology and cancer. Oncogene 29, 313-324 (2010).
7. Herranz, D. et al. Metabolic reprogramming induces resistance to anti-NOTCH1 therapies in T cell acute lymphoblastic leukemia. Nat Med 21, 1182-1189 (2015).
8. Yuneva, M. O. et al. The metabolic profile of tumors depends on both the responsible genetic lesion and tissue type. Cell Metab 15, 157-170 (2012).
9. Gao, P. et al. c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism. Nature 458, 762-765 (2009).
10. Weinberg, F. et al. Mitochondrial metabolism and ROS generation are essential for Kras-mediated tumorigenicity. Proc Natl Acad Sci USA 107, 8788-8793 (2010).
11. Trachootham, D., Lu, W., Ogasawara, M. A., Nilsa, R. D. & Huang, P. Redox regulation of cell survival. Antioxid Redox Signal 10, 1343-1374 (2008).
12. Vafa, O. et al. c-Myc can induce DNA damage, increase reactive oxygen species, and mitigate p53 function: a mechanism for oncogene-induced genetic instability. Mol Cell 9, 1031-1044 (2002).
13. Achanta, G. et al. Novel role of p53 in maintaining mitochondrial genetic stability through interaction with DNA Pol gamma. EMBO J 24, 3482-3492 (2005).
14. Lee, S. R. et al. Reversible inactivation of the tumor suppressor PTEN by H2O2. J Biol Chem 277, 20336-20342 (2002).
15. Kwon, J. et al. Reversible oxidation and inactivation of the tumor suppressor PTEN in cells stimulated with peptide growth factors. Proc Natl Acad Sci USA 101, 16419-16424 (2004).
16. Rhee, S. G. et al. Intracellular messenger function of hydrogen peroxide and its regulation by peroxiredoxins. Curr Opin Cell Biol 17, 183-189 (2005).
17. Finkel, T. & Holbrook, N. J. Oxidants, oxidative stress and the biology of ageing. Nature 408, 239-247 (2000).
18. Trachootham, D. et al. Selective killing of oncogenically transformed cells through a ROS-mediated mechanism by beta-phenylethyl isothiocyanate. Cancer Cell 10, 241-252 (2006).
19. Raj, L. et al. Selective killing of cancer cells by a small molecule targeting the stress response to ROS. Nature 475, 231-234 (2011).
20. Shaw, A. T. et al. Selective killing of K-ras mutant cancer cells by small molecule inducers of oxidative stress. Proc Natl Acad Sci USA 108, 8773-8778 (2011).
21. Trachootham, D., Alexandre, J. & Huang, P. Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat Rev Drug Discov 8, 579-591 (2009).
22. Cairns, R. A., Harris, I. S. & Mak, T. W. Regulation of cancer cell metabolism. Nat Rev Cancer 11, 85-95 (2011).
23. Son, J. et al. Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway. Nature 496, 101-105 (2013).
24. Barretina, J. et al. The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature 483, 603-607 (2012).
25. Chiu, M. et al. Glutamine depletion by crisantaspase hinders the growth of human hepatocellular carcinoma xenografts. Br J Cancer 111, 1159-1167 (2014).
26. Schmidt, A. et al. Differential expression of glutamine synthetase and cytochrome P450 isoforms in human hepatoblastoma. Toxicology 281, 7-14 (2011).
27. van den Heuvel, A. P., Jing, J., Wooster, R. F. & Bachman, K. E. Analysis of glutamine dependency in non-small cell lung cancer: GLS1 splice variant GAC is essential for cancer cell growth. Cancer Biol Ther 13, 1185-1194 (2012).
28. Le, A. et al. Glucose-independent glutamine metabolism via TCA cycling for proliferation and survival in B cells. Cell Metab 15, 110-121 (2012).
29. Sadzuka, Y., Yamashita, Y. & Sonobe, T. Effects of glutamate transporter inhibitors on the antitumor activity of doxorubicin. Clin Cancer Res 8, 3943-3947 (2002).
30. Pedraz-Cuesta, E. et al. The glutamate transport inhibitor DL-Threo-beta-Benzyloxyaspartic acid (DL-TBOA) differentially affects SN38- and oxaliplatin-induced death of drug-resistant colorectal cancer cells. BMC Cancer 15, 411 (2015).
31. Hagen, T. M., Aw, T. Y. & Jones, D. P. Glutathione uptake and protection against oxidative injury in isolated kidney cells. Kidney Int 34, 74-81 (1988).
32. Lash, L. H., Hagen, T. M. & Jones, D. P. Exogenous glutathione protects intestinal epithelial cells from oxidative injury. Proc Natl Acad Sci USA 83, 4641-4645 (1986).
33. Simbulan-Rosenthal, C. M., Rosenthal, D. S., Iyer, S., Boulares, A. H. & Smulson, M. E. Transient poly(ADP-ribosyl)ation of nuclear proteins and role of poly(ADP-ribose) polymerase in the early stages of apoptosis. J Biol Chem 273, 13703-13712 (1998).
34. Bonner, W. M. et al. GammaH2AX and cancer. Nat Rev Cancer 8, 957-967 (2008).
35. Loike, J. D. & Horwitz, S. B. Effect of VP-16-213 on the intracellular degradation of DNA in HeLa cells. Biochemistry 15, 5443-5448 (1976).
36. Wozniak, A. J. & Ross, W. E. DNA damage as a basis for 4′ -demethylepipodophyllotoxin-9-(4,6-O-ethylidene-beta-D-glucopyranoside) (etoposide) cytotoxicity. Cancer Res 43, 120-124 (1983).
37. Nicolay, B. N. et al. Loss of RBF1 changes glutamine catabolism. Genes Dev 27, 182-196 (2013).
38. Cheng, T. et al. Pyruvate carboxylase is required for glutamine-independent growth of tumor cells. Proc Natl Acad Sci USA 108, 8674-8679 (2011).
39. Linn, T. C., Pettit, F. H. & Reed, L. J. Alpha-keto acid dehydrogenase complexes. X. Regulation of the activity of the pyruvate dehydrogenase complex from beef kidney mitochondria by phosphorylation and dephosphorylation. Proc Natl Acad Sci USA 62, 234-241 (1969).
40. Kolobova, E., Tuganova, A., Boulatnikov, I. & Popov, K. M. Regulation of pyruvate dehydrogenase activity through phosphorylation at multiple sites. Biochem J 358, 69-77 (2001).
41. Sugden, M. C. & Holness, M. J. Mechanisms underlying regulation of the expression and activities of the mammalian pyruvate dehydrogenase kinases. Arch Physiol Biochem 112, 139-149 (2006).
42. Bowker-Kinley, M. M., Davis, W. I., Wu, P., Harris, R. A. & Popov, K. M. Evidence for existence of tissue-specific regulation of the mammalian pyruvate dehydrogenase complex. Biochem J 329 (Pt 1), 191-196 (1998).
43. Adams, D. J. et al. Synthesis, cellular evaluation, and mechanism of action of piperlongumine analogs. Proc Natl Acad Sci USA 109, 15115-15120 (2012).
44. Yuneva, M., Zamboni, N., Oefner, P., Sachidanandam, R. & Lazebnik, Y. Deficiency in glutamine but not glucose induces MYCdependent apoptosis in human cells. J Cell Biol 178, 93-105 (2007).
45. Shanware, N. P., Mullen, A. R., DeBerardinis, R. J. & Abraham, R. T. Glutamine: pleiotropic roles in tumor growth and stress resistance. J Mol Med (Berl) 89, 229-236 (2011).
46. Gorrini, C., Harris, I. S. & Mak, T. W. Modulation of oxidative stress as an anticancer strategy. Nat Rev Drug Discov 12, 931-947 (2013).
47. Marin-Valencia, I. et al. Analysis of tumor metabolism reveals mitochondrial glucose oxidation in genetically diverse human glioblastomas in the mouse brain in vivo. Cell Metab 15, 827-837 (2012).
48. Jeon, S. M., Chandel, N. S. & Hay, N. AMPK regulates NADPH homeostasis to promote tumour cell survival during energy stress. Nature 485, 661-665 (2012).
49. Wellen, K. E. et al. The hexosamine biosynthetic pathway couples growth factor-induced glutamine uptake to glucose metabolism. Genes Dev 24, 2784-2799 (2010).
50. Wise, D. R. et al. Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction. Proc Natl Acad Sci USA 105, 18782-18787 (2008).
51. Fernandez, C. A., Des Rosiers, C., Previs, S. F., David, F. & Brunengraber, H. Correction of 13C mass isotopomer distributions for natural stable isotope abundance. J Mass Spectrom 31, 255-262 (1996).