Oncogenic PI3K and K-Ras stimulate de novo lipid synthesis through mTORC1 and SREBP

Oncogene

Volumn 35, Issue 10, 2016, Pages 1250-1260

  Ricoult, S J H ^a   Yecies, J L ^a,b   Ben Sahra, I ^a   Manning, B D ^a  

^a HARVARD SCHOOL OF PUBLIC HEALTH   (United States)

^b GENENTECH INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GROWTH FACTOR; K RAS PROTEIN; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; PHOSPHATIDYLINOSITOL 3 KINASE; STEROL REGULATORY ELEMENT BINDING PROTEIN 1; STEROL REGULATORY ELEMENT BINDING PROTEIN 2; KRAS PROTEIN, HUMAN; MECHANISTIC TARGET OF RAPAMYCIN COMPLEX 1; MULTIPROTEIN COMPLEX; PROTEIN P21; TARGET OF RAPAMYCIN KINASE;

ARTICLE; BREAST CANCER CELL LINE; CANCER CELL; CANCER GROWTH; CELL PROLIFERATION; CONTROLLED STUDY; GENE EXPRESSION; HUMAN; HUMAN CELL; LIPOGENESIS; MOLECULAR MECHANICS; ONCOGENE; PRIORITY JOURNAL; ANIMAL; GENE EXPRESSION REGULATION; METABOLISM; MOUSE; SIGNAL TRANSDUCTION; TUMOR CELL LINE;

ANIMALS; CELL LINE, TUMOR; CELL PROLIFERATION; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; LIPOGENESIS; MICE; MULTIPROTEIN COMPLEXES; PHOSPHATIDYLINOSITOL 3-KINASES; PROTO-ONCOGENE PROTEINS P21(RAS); SIGNAL TRANSDUCTION; STEROL REGULATORY ELEMENT BINDING PROTEIN 1; STEROL REGULATORY ELEMENT BINDING PROTEIN 2; TOR SERINE-THREONINE KINASES;

EID: 84930328718     PISSN: 09509232     EISSN: 14765594     Source Type: Journal    
DOI: 10.1038/onc.2015.179     Document Type: Article

References (65)

1. Medes G Thomas A, Weinhouse S. Metabolism of neoplastic tissue. IV. A study of lipid synthesis in neoplastic tissue slices in vitro. Cancer Res 1953; 13: 27-29
2. Menendez JA Lupu R. Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis. Nat Rev Cancer 2007; 7: 763-777
3. Santos CR Schulze A. Lipid metabolism in cancer. FEBS J 2012; 279: 2610-2623
4. Kuhajda FP, Jennert K, Wood FD, Hennigart RA, Jacobs LB, Dick JD et al. Fatty acid synthesis : a potential selective target for antineoplastic therapy. Proc Natl Acad Sci USA 1994; 91: 6379-6383
5. Li J, Ding S, Habib N, Fermor B, Wood C, Gilmour R. Partial characterization of a cDNA for human stearoyl-CoA desaturase and changes in its mRNA expression in some normal and malignant tissues. Int J Cancer 1994; 57: 348-352
6. Horton JD, Goldstein JL, Brown MS. SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest 2002; 109: 1125-1131
7. Wang X, Sato R, Brown MS, Hua X, Goldsteln JL. SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysis. Cell 1994; 77: 53-62
8. Hua X, Sakai J, Brown MS, Goldstein JL. Regulated cleavage of sterol regulatory element binding proteins requires sequences on both sides of the endoplasmic reticulum membrane. J Biol Chem 1996; 271: 10379-10384
9. Sakai J, Duncan EA, Rawson RB, Hua X, Brown MS, Goldstein JL. Sterol-regulated release of SREBP-2 from cell membranes requires two sequential cleavages, one within a transmembrane segment. Cell 1996; 85: 1037-1046
10. Goldstein JL, DeBose-Boyd RA, Brown MS. Protein sensors for membrane sterols. Cell 2006; 124: 35-46
11. Jeon T, Osborne TF. SREBPs: metabolic integrators in physiology and metabolism. Trends Endocrinol Metab 2011; 23: 65-72
12. Ricoult SJH, Manning BD. The multifaceted role of mTORC1 in the control of lipid metabolism. EMBO Rep 2013; 14: 242-251
13. Düvel K, Yecies JL, Menon S, Raman P, Lipovsky AI, Souza AL et al. Activation of a metabolic gene regulatory network downstream of mTOR complex 1. Mol Cell 2010; 39: 171-183
14. Porstmann T, Santos CR, Griffiths B, Cully M, Wu M, Leevers S et al. SREBP activity is regulated by mTORC1 and contributes to Akt-dependent cell growth. Cell Metab 2008; 8: 224-236
15. Li S, Brown MS, Goldstein JL. Bifurcation of insulin signaling pathway in rat liver: mTORC1 required for stimulation of lipogenesis, but not inhibition of gluconeogenesis. Proc Natl Acad Sci USA 2010; 107: 3441-3446
16. Yecies JL, Zhang HH, Menon S, Liu S, Yecies D, Lipovsky AI et al. Akt stimulates hepatic SREBP1c and lipogenesis through parallel mTORC1-dependent and independent pathways. Cell Metab 2011; 14: 21-32
17. Li S, Ogawa W, Emi A, Hayashi K, Senga Y, Nomura K et al. Role of S6K1 in regulation of SREBP1c expression in the liver. Biochem Biophys Res Commun 2011; 412: 197-202
18. Wang BT, Ducker GS, Barczak AJ, Barbeau R, Erle DJ, Shokat KM. The mammalian target of rapamycin regulates cholesterol biosynthetic gene expression and exhibits a rapamycin-resistant transcriptional profile. Proc Natl Acad Sci USA 2011; 108: 15201-15206
19. Liu X, Yuan H, Niu Y, Niu W, Fu L. The role of AMPK/mTOR/S6K1 signaling axis in mediating the physiological process of exercise-induced insulin sensitization in skeletal muscle of C57BL/6 mice. Biochim Biophys Acta 2012; 1822: 1716-1726
20. Owen JL, Zhang Y, Bae S-H, Farooqi MS, Liang G, Hammer RE et al. Insulin stimulation of SREBP-1c processing in transgenic rat hepatocytes requires p70 S6-kinase. Proc Natl Acad Sci USA 2012; 109: 16184-16189
21. Luyimbazi D, Akcakanat A, McAuliffe PF, Zhang L, Singh G, Gonzalez-Angulo AM et al. Rapamycin regulates stearoyl CoA desaturase 1 expression in breast cancer. Mol Cancer Ther 2010; 9: 2770-2784
22. Peterson TR, Sengupta SS, Harris TE, Carmack AE, Kang SA, Balderas E et al. mTOR complex 1 regulates lipin 1 localization to control the SREBP pathway. Cell 2011; 146: 408-420
23. Feldman ME, Apsel B, Uotila A, Loewith R, Knight ZA, Ruggero D et al. Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2. PLoS Biol 2009; 7: e1000038
24. Thoreen CC, Kang SA, Chang JW, Liu Q, Zhang J, Gao Y et al. An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1. J Biol Chem 2009; 284: 8023-8032
25. Dibble CC, Elis W, Menon S, Qin W, Klekota J, Asara JM et al. TBC1D7 is a third subunit of the TSC1-TSC2 complex upstream of mTORC1. Mol Cell 2012; 47: 535-546
26. Dibble CC, Manning BD. Signal integration by mTORC1 coordinates nutrient input with biosynthetic output. Nat Cell Biol 2013; 15: 555-564
27. Huang J, Manning BD. The TSC1-TSC2 complex: a molecular switchboard controlling cell growth. Biochem J 2008; 412: 179-190
28. Crino PB, Nathanson KL, Henske EP. The tuberous sclerosis complex. N Engl J Med 2006; 355: 1345-1356
29. Menon S, Manning BD. Common corruption of the mTOR signaling network in human tumors. Oncogene 2008; 27: S43-S51
30. Manning BD, Tee AR, Logsdon MN, Blenis J, Cantley LC. Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway. Mol Cell 2002; 10: 151-162
31. Inoki K, Li Y, Zhu T, Wu J, Guan K. TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat Cell Biol 2002; 4: 648-657
32. Johannessen CM, Reczek EE, James MF, Brems H, Legius E, Cichowski K. The NF1 tumor suppressor critically regulates TSC2 and mTOR. Proc Natl Acad Sci USA 2005; 102: 8573-8578
33. Ma L, Chen Z, Erdjument-Bromage H, Tempst P, Pandolfi PP. Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis. Cell 2005; 121: 179-193
34. Roux PP, Ballif BA, Anjum R, Gygi SP, Blenis J. Tumor-promoting phorbol esters and activated Ras inactivate the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 kinase. Proc Natl Acad Sci USA 2004; 101: 13489-13494
35. Tweto J, Liberati M, Larrabee A. Protein turnover and 4?-phosphopantetheine exchange in rat liver fatty acid synthetase. J Biol Chem 1971; 246: 2468-2471
36. Nakanishi S, Numa S. Purification of rat liver acetyl coenzyme A carboxylase and immunochemical studies on its synthesis and degradation. Eur J Biochem 1970; 16: 161-173
37. Griffiths B, Lewis CA, Bensaad K, Ros S, Zhang Q, Ferber EC et al. Sterol regulatory element binding protein-dependent regulation of lipid synthesis supports cell survival and tumor growth. Cancer Metab 2013; 1: 3
38. Kidani Y, Elsaesser H, Hock MB, Vergnes L, Williams KJ, Argus JP et al. Sterol regulatory element-binding proteins are essential for the metabolic programming of effector T cells and adaptive immunity. Nat Immunol 2013; 14: 489-499
39. Amemiya-Kudo M, Shimano H, Yoshikawa T, Yahagi N, Hasty AH, Okazaki H et al. Promoter analysis of the mouse sterol regulatory element-binding protein-1c gene. J Biol Chem 2000; 275: 31078-31085
40. Cancer Genome Atlas Network, Comprehensive molecular portraits of human breast tumours Nature 2012 490 61-70
41. Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov 2012; 2: 401-404
42. Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal 2013; 6: pl1
43. Howell JJ, Ricoult SJH, Ben-Sahra I, Manning BD. A growing role for mTOR in promoting anabolic metabolism. Biochem Soc Trans 2013; 41: 906-912
44. Porstmann T, Griffiths B, Chung Y-L, Delpuech O, Griffiths JR, Downward J et al. PKB/Akt induces transcription of enzymes involved in cholesterol and fatty acid biosynthesis via activation of SREBP. Oncogene 2005; 24: 6465-6481
45. Guo D, Prins RRM, Dang J, Kuga D, Iwanami A, Soto H et al. EGFR signaling through an Akt-SREBP-1-dependent, rapamycin-resistant pathway sensitizes glioblastomas to antilipogenic therapy. Sci Signal 2009; 2: ra82
46. Krycer JRJ, Phan L, Brown AJA. A key regulator of cholesterol homeostasis, SREBP-2, can be targeted in prostate cancer cells with natural products. Biochem J 2012; 446: 191-201
47. Williams KJ, Argus JP, Zhu Y, Wilks MQ, Marbois BN, York AG et al. An essential requirement for the SCAP/SREBP signaling axis to protect cancer cells from lipotoxicity. Cancer Res 2013; 73: 2850-2862
48. Shimano H, Shimomura I, Hammer RE, Herz J, Goldstein JL, Brown MS et al. Elevated levels of SREBP-2 and cholesterol synthesis in livers of mice homozygous for a targeted disruption of the SREBP-1 gene. J Clin Invest 1997; 100: 2115-2124
49. Hatzivassiliou G, Zhao F, Bauer DE, Andreadis C, Shaw AN, Dhanak D et al. ATP citrate lyase inhibition can suppress tumor cell growth. Cancer Cell 2005; 8: 311-321
50. Migita T, Narita T, Nomura K, Miyagi E, Inazuka F, Matsuura M et al. ATP citrate lyase: activation and therapeutic implications in non-small cell lung cancer. Cancer Res 2008; 68: 8547-8554
51. Fritz V, Benfodda Z, Rodier G, Henriquet C, Iborra F, Avancès C et al. Abrogation of de novo lipogenesis by stearoyl-CoA desaturase 1 inhibition interferes with oncogenic signaling and blocks prostate cancer progression in mice. Mol Cancer Ther 2010; 9: 1740-1754
52. Roongta UV, Pabalan JG, Wang X, Ryseck R-P, Fargnoli J, Henley BJ et al. Cancer cell dependence on unsaturated fatty acids implicates stearoyl-CoA desaturase as a target for cancer therapy. Mol Cancer Res 2011; 9: 1551-1561
53. Minville-Walz M, Pierre A-S, Pichon L, Bellenger S, Fèvre C, Bellenger J et al. Inhibition of stearoyl-CoA desaturase 1 expression induces CHOP-dependent cell death in human cancer cells. PLoS One 2010; 5: e14363
54. Young RM, Ackerman D, Quinn ZL, Mancuso A, Gruber M, Liu L et al. Dysregulated mTORC1 renders cells critically dependent on desaturated lipids for survival under tumor-like stress. Genes Dev 2013; 27: 1115-1131
55. Freed-Pastor WA, Mizuno H, Zhao X, Langerød A, Moon S-H, Rodriguez-Barrueco R et al. Mutant p53 disrupts mammary tissue architecture via the mevalonate pathway. Cell 2012; 148: 244-258
56. Clendening JW, Penn LZ. Targeting tumor cell metabolism with statins. Oncogene 2012; 31: 4967-4978
57. Kamphorst JJ, Cross JR, Fan J, de Stanchina E, Mathew R, White EP et al. Hypoxic and Ras-transformed cells support growth by scavenging unsaturated fatty acids from lysophospholipids. Proc Natl Acad Sci USA 2013; 110: 8882-8887
58. Morrisett JD, Abdel-Fattah G, Hoogeveen R, Mitchell E, Ballantyne CM, Pownall HJ et al. Effects of sirolimus on plasma lipids, lipoprotein levels, and fatty acid metabolism in renal transplant patients. J Lipid Res 2002; 43: 1170-1180
59. Kasiske BL, de Mattos A, Flechner SM, Gallon L, Meier-Kriesche HU, Weir MR et al. Mammalian target of rapamycin inhibitor dyslipidemia in kidney transplant recipients. Am J Transpl 2008; 8: 1384-1392
60. Zhang C, Yoon M-S, Chen J. Amino acid-sensing mTOR signaling is involved in modulation of lipolysis by chronic insulin treatment in adipocytes. Am J Physiol Endocrinol Metab 2009; 296: E862-E868
61. Chakrabarti P, English T, Shi J, Smas CM, Kandror KV. Mammalian target of rapamycin complex 1 suppresses lipolysis, stimulates lipogenesis, and promotes fat storage. Diabetes 2010; 59: 775-781
62. Soliman GA, Acosta-Jaquez HA, Fingar DC. mTORC1 inhibition via rapamycin promotes triacylglycerol lipolysis and release of free fatty acids in 3T3-L1 adipocytes. Lipids 2010; 45: 1089-1100
63. Zhao JJ, Liu Z, Wang L, Shin E, Loda MF, Roberts TM. The oncogenic properties of mutant p110alpha and p110beta phosphatidylinositol 3-kinases in human mammary epithelial cells. Proc Natl Acad Sci USA 2005; 102: 18443-18448
64. Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods 2012; 9: 671-675
65. Neve RM, Chin K, Fridlyand J, Yeh J, Frederick L, Fevr T et al. A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. Cancer Cell 2006; 10: 515-527