Nrf2 Redirects Glucose and Glutamine into Anabolic Pathways in Metabolic Reprogramming

Cancer Cell

Volumn 22, Issue 1, 2012, Pages 66-79

  Mitsuishi, Yoichiro ^a   Taguchi, Keiko ^a   Kawatani, Yukie ^a   Shibata, Tatsuhiro ^b   Nukiwa, Toshihiro ^a   Aburatani, Hiroyuki ^c   Yamamoto, Masayuki ^a   Motohashi, Hozumi ^a  

^a TOHOKU UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

^b NATIONAL CANCER CENTER RESEARCH INSTITUTE   (Japan)

^c UNIVERSITY OF TOKYO   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

GLUCOSE; GLUTAMINE; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; TRANSCRIPTION FACTOR NRF2;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CANCER CELL; CELL DIFFERENTIATION; CELL EXPANSION; CELL PROLIFERATION; CELL PROTECTION; CONTROLLED STUDY; GLUCOSE METABOLISM; HUMAN; HUMAN CELL; LUNG ADENOCARCINOMA; MALE; MOUSE; NONHUMAN; NUCLEAR REPROGRAMMING; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN METABOLISM; PROTEIN PROTEIN INTERACTION; PROTEIN SYNTHESIS; SIGNAL TRANSDUCTION;

EID: 84863764614     PISSN: 15356108     EISSN: 18783686     Source Type: Journal    
DOI: 10.1016/j.ccr.2012.05.016     Document Type: Article

References (47)

1. Bea F., Hudson F.N., Chait A., Kavanagh T.J., Rosenfeld M.E. Induction of glutathione synthesis in macrophages by oxidized low-density lipoproteins is mediated by consensus antioxidant response elements. Circ. Res. 2003, 92:386-393.
2. Bensaad K., Tsuruta A., Selak M.A., Vidal M.N., Nakano K., Bartrons R., Gottlieb E., Vousden K.H. TIGAR, a p53-inducible regulator of glycolysis and apoptosis. Cell 2006, 126:107-120.
3. Beyer T.A., Xu W., Teupser D., auf dem Keller U., Bugnon P., Hildt E., Thiery J., Kan Y.W., Werner S. Impaired liver regeneration in Nrf2 knockout mice: role of ROS-mediated insulin/IGF-1 resistance. EMBO J. 2008, 27:212-223.
4. Casamayor A., Morrice N.A., Alessi D.R. Phosphorylation of Ser-241 is essential for the activity of 3-phosphoinositide-dependent protein kinase-1: identification of five sites of phosphorylation in vivo. Biochem. J. 1999, 342:287-292.
5. Cross D.A.E., Alessi D.R., Cohen P., Andjelkovich M., Hemmings B.A. Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature 1995, 378:785-789.
6. Dang C.V. Glutaminolysis: supplying carbon or nitrogen or both for cancer cells?. Cell Cycle 2010, 9:3884-3886.
7. 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.
8. DeBerardinis R.J., Lum J.J., Hatzivassiliou G., Thompson C.B. The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab. 2008, 7:11-20.
9. 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.
10. Elstrom R.L., Bauer D.E., Buzzai M., Karnauskas R., Harris M.H., Plas D.R., Zhuang H., Cinalli R.M., Alavi A., Rudin C.M., Thompson C.B. Akt stimulates aerobic glycolysis in cancer cells. Cancer Res. 2004, 64:3892-3899.
11. Engelman J.A. Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat. Rev. Cancer 2009, 9:550-562.
12. Harrison E.M., McNally S.J., Devey L., Garden O.J., Ross J.A., Wigmore S.J. Insulin induces heme oxygenase-1 through the phosphatidylinositol 3-kinase/Akt pathway and the Nrf2 transcription factor in renal cells. FEBS J. 2006, 273:2345-2356.
13. Horie Y., Suzuki A., Kataoka E., Sasaki T., Hamada K., Sasaki J., Mizuno K., Hasegawa G., Kishimoto H., Iizuka M., et al. Hepatocyte-specific Pten deficiency results in steatohepatitis and hepatocellular carcinomas. J. Clin. Invest. 2004, 113:1774-1783.
14. Ishimoto T., Nagano O., Yae T., Tamada M., Motohara T., Oshima H., Oshima M., Ikeda T., Asaba R., Yagi H., et al. CD44 variant regulates redox status in cancer cells by stabilizing the xCT subunit of system xc(-) and thereby promotes tumor growth. Cancer Cell 2011, 19:387-400.
15. Itoh K., Chiba T., Takahashi S., Ishii T., Igarashi K., Katoh Y., Oyake T., Hayashi N., Satoh K., Hatayama I., et al. An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem. Biophys. Res. Commun. 1997, 236:313-322.
16. Kim Y.R., Oh J.E., Kim M.S., Kang M.R., Park S.W., Han J.Y., Eom H.S., Yoo N.J., Lee S.H. Oncogenic NRF2 mutations in squamous cell carcinomas of oesophagus and skin. J. Pathol. 2010, 220:446-451.
17. Kroemer G., Pouyssegur J. Tumor cell metabolism: cancer's Achilles' heel. Cancer Cell 2008, 13:472-482.
18. Li J., Yen C., Liaw D., Podsypanina K., Bose S., Wang S.I., Puc J., Miliaresis C., Rodgers L., McCombie R., et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 1997, 275:1943-1947.
19. Lu S.C. Regulation of glutathione synthesis. Mol. Aspects Med. 2009, 30:42-59.
20. MacLeod A.K., McMahon M., Plummer S.M., Higgins L.G., Penning T.M., Igarashi K., Hayes J.D. Characterization of the cancer chemopreventive NRF2-dependent gene battery in human keratinocytes: demonstration that the KEAP1-NRF2 pathway, and not the BACH1-NRF2 pathway, controls cytoprotection against electrophiles as well as redox-cycling compounds. Carcinogenesis 2009, 30:1571-1580.
21. Malhotra D., Portales-Casamar E., Singh A., Srivastava S., Arenillas D., Happel C., Shyr C., Wakabayashi N., Kensler T.W., Wasserman W.W., Biswal S. Global mapping of binding sites for Nrf2 identifies novel targets in cell survival response through ChIP-Seq profiling and network analysis. Nucleic Acids Res. 2010, 38:5718-5734.
22. Moinova H.R., Mulcahy R.T. Up-regulation of the human gamma-glutamylcysteine synthetase regulatory subunit gene involves binding of Nrf-2 to an electrophile responsive element. Biochem. Biophys. Res. Commun. 1999, 261:661-668.
23. Okawa H., Motohashi H., Kobayashi A., Aburatani H., Kensler T.W., Yamamoto M. Hepatocyte-specific deletion of the keap1 gene activates Nrf2 and confers potent resistance against acute drug toxicity. Biochem. Biophys. Res. Commun. 2006, 339:79-88.
24. Rada P., Rojo A.I., Chowdhry S., McMahon M., Hayes J.D., Cuadrado A. SCF/beta-TrCP promotes glycogen synthase kinase 3-dependent degradation of the Nrf2 transcription factor in a Keap1-independent manner. Mol. Cell. Biol. 2011, 31:1121-1133.
25. Reddy N.M., Kleeberger S.R., Cho H.Y., Yamamoto M., Kensler T.W., Biswal S., Reddy S.P. Deficiency in Nrf2-GSH signaling impairs type II cell growth and enhances sensitivity to oxidants. Am. J. Respir. Cell Mol. Biol. 2007, 37:3-8.
26. Reddy N.M., Kleeberger S.R., Bream J.H., Fallon P.G., Kensler T.W., Yamamoto M., Reddy S.P. Genetic disruption of the Nrf2 compromises cell-cycle progression by impairing GSH-induced redox signaling. Oncogene 2008, 27:5821-5832.
27. Sakamoto K., Iwasaki K., Sugiyama H., Tsuji Y. Role of the tumor suppressor PTEN in antioxidant responsive element-mediated transcription and associated histone modifications. Mol. Biol. Cell 2009, 20:1606-1617.
28. Sasaki H., Sato H., Kuriyama-Matsumura K., Sato K., Maebara K., Wang H., Tamba M., Itoh K., Yamamoto M., Bannai S. Electrophile response element-mediated induction of the cystine/glutamate exchange transporter gene expression. J. Biol. Chem. 2002, 277:44765-44771.
29. Sekhar K.R., Crooks P.A., Sonar V.N., Friedman D.B., Chan J.Y., Meredith M.J., Starnes J.H., Kelton K.R., Summar S.R., Sasi S., Freeman M.L. NADPH oxidase activity is essential for Keap1/Nrf2-mediated induction of GCLC in response to 2-indol-3-yl-methylenequinuclidin-3-ols. Cancer Res. 2003, 63:5636-5645.
30. Shibata T., Ohta T., Tong K.I., Kokubu A., Odogawa R., Tsuta K., Asamura H., Yamamoto M., Hirohashi S. Cancer related mutations in NRF2 impair its recognition by Keap1-Cul3 E3 ligase and promote malignancy. Proc. Natl. Acad. Sci. USA 2008, 105:13568-13573.
31. Singh A., Misra V., Thimmulappa R.K., Lee H., Ames S., Hoque M.O., Herman J.G., Baylin S.B., Sidransky D., Gabrielson E., et al. Dysfunctional KEAP1-NRF2 interaction in non-small-cell lung cancer. PLoS Med. 2006, 3:e420.
32. Singh A., Boldin-Adamsky S., Thimmulappa R.K., Rath S.K., Ashush H., Coulter J., Blackford A., Goodman S.N., Bunz F., Watson W.H., et al. RNAi-mediated silencing of nuclear factor erythroid-2-related factor 2 gene expression in non-small cell lung cancer inhibits tumor growth and increases efficacy of chemotherapy. Cancer Res. 2008, 68:7975-7984.
33. So H.S., Kim H.J., Lee J.H., Lee J.H., Park S.Y., Park C., Kim Y.H., Kim J.K., Lee K.M., Kim K.S., et al. Flunarizine induces Nrf2-mediated transcriptional activation of heme oxygenase-1 in protection of auditory cells from cisplatin. Cell Death Differ. 2006, 13:1763-1775.
34. Solis W.A., Dalton T.P., Dieter M.Z., Freshwater S., Harrer J.M., He L., Shertzer H.G., Nebert D.W. Glutamate-cysteine ligase modifier subunit: mouse Gclm gene structure and regulation by agents that cause oxidative stress. Biochem. Pharmacol. 2002, 63:1739-1754.
35. Solis L.M., Behrens C., Dong W., Suraokar M., Ozburn N.C., Moran C.A., Corvalan A.H., Biswal S., Swisher S.G., Bekele B.N., et al. Nrf2 and Keap1 abnormalities in non-small cell lung carcinoma and association with clinicopathologic features. Clin. Cancer Res. 2010, 16:3743-3753.
36. Taguchi K., Shimada M., Fujii S., Sumi D., Pan X., Yamano S., Nishiyama T., Hiratsuka A., Yamamoto M., Cho A.K., et al. Redox cycling of 9,10-phenanthraquinone to cause oxidative stress is terminated through its monoglucuronide conjugation in human pulmonary epithelial A549 cells. Free Radic. Biol. Med. 2008, 44:1645-1655.
37. Taguchi K., Maher J.M., Suzuki T., Kawatani Y., Motohashi H., Yamamoto M. Genetic analysis of cytoprotective functions supported by graded expression of Keap1. Mol. Cell. Biol. 2010, 30:3016-3026.
38. Taub R. Liver regeneration: from myth to mechanism. Nat. Rev. Mol. Cell Biol. 2004, 5:836-847.
39. Thimmulappa R.K., Mai K.H., Srisuma S., Kensler T.W., Yamamoto M., Biswal S. Identification of Nrf2-regulated genes induced by the chemopreventive agent sulforaphane by oligonucleotide microarray. Cancer Res. 2002, 62:5196-5203.
40. Tong X., Zhao F., Thompson C.B. The molecular determinants of de novo nucleotide biosynthesis in cancer cells. Curr. Opin. Genet. Dev. 2009, 19:32-37.
41. Uruno A., Motohashi H. The Keap1-Nrf2 system as an in vivo sensor for electrophiles. Nitric Oxide 2011, 25:153-160.
42. Wakabayashi N., Itoh K., Wakabayashi J., Motohashi H., Noda S., Takahashi S., Imakado S., Kotsuji T., Otsuka F., Roop D.R., et al. Keap1-null mutation leads to postnatal lethality due to constitutive Nrf2 activation. Nat. Genet. 2003, 35:238-245.
43. Wang R., An J., Ji F., Jiao H., Sun H., Zhou D. Hypermethylation of the Keap1 gene in human lung cancer cell lines and lung cancer tissues. Biochem. Biophys. Res. Commun. 2008, 373:151-154.
44. Wu K.C., Cui J.Y., Klaassen C.D. Beneficial role of Nrf2 in regulating NADPH generation and consumption. Toxicol. Sci. 2011, 123:590-600.
45. Yuan T.L., Cantley L.C. PI3K pathway alterations in cancer: variations on a theme. Oncogene 2008, 27:5497-5510.
46. Zhang J., Hosoya T., Maruyama A., Nishikawa K., Maher J.M., Ohta T., Motohashi H., Fukamizu A., Shibahara S., Itoh K., Yamamoto M. Nrf2 Neh5 domain is differentially utilized in the transactivation of cytoprotective genes. Biochem. J. 2007, 404:459-466.
47. Zhang P., Singh A., Yegnasubramanian S., Esopi D., Kombairaju P., Bodas M., Wu H., Bova S.G., Biswal S. Loss of Kelch-like ECH-associated protein 1 function in prostate cancer cells causes chemoresistance and radioresistance and promotes tumor growth. Mol. Cancer Ther. 2010, 9:336-346.