The Lipogenic Switch in Cancer

Chapter

Abbreviations

ACBP

Acyl-CoA binding protein

ACC-alpha

Acetyl-CoA carboxylase-alpha

ACL

ATP citrate lyase

AMPK

Adenosine monophosphate-activated kinase

BRCA1

Breast cancer susceptibility gene 1

CPT-1

Carnitine palmitoyltransferase-1

FABP

Fatty acid binding protein

FASN

Fatty acid synthase

FATP

Fatty acid transport protein

HMG-CoA

Hydroxymethylglutaryl-CoA

LDL

Low density lipoprotein

LPL

Lipoprotein lipase

MAPK

Mitogen-activated protein kinase

PI3K

Phosphaditylinositol 3′-kinase

PTEN

Phosphatase and tensin homologue deleted on chromosome 10

RNAi

RNA interference

SCAP

SREBP cleavage-activating protein

SREBP

Sterol regulatory element-binding protein

TOFA

5-(Tetradecyloxy)-2-furoic acid

References

  1. Abu-Elheiga, L., Matzuk, M. M., Kordari, P., Oh, W., Shaikenov, T., Gu, Z. and Wakil, S. J. 2005. Mutant mice lacking acetyl-CoA carboxylase 1 are embryonically lethal. Proc Natl Acad Sci USA 102: 12011–12016.PubMedCrossRefGoogle Scholar
  2. Alli, P. M., Pinn, M. L., Jaffee, E. M., McFadden, J. M. and Kuhajda, F. P. 2005. Fatty acid synthase inhibitors are chemopreventive for mammary cancer in neu-N transgenic mice. Oncogene 24: 39–46.PubMedCrossRefGoogle Scholar
  3. Alo, P. L., Visca, P., Marci, A., Mangoni, A., Botti, C. and Di Tondo, U. 1996. Expression of fatty acid synthase (FAS) as a predictor of recurrence in stage I breast carcinoma patients. Cancer 77: 474–482.PubMedCrossRefGoogle Scholar
  4. Altomare, D. A. and Testa, J. R. 2005. Perturbations of the AKT signaling pathway in human cancer. Oncogene 24: 7455–7464.PubMedCrossRefGoogle Scholar
  5. Bandyopadhyay, S., Pai, S. K., Watabe, M., Gross, S. C., Hirota, S., Hosobe, S., Tsukada, T., Miura, K., Saito, K., Markwell, S. J., Wang, Y., Huggenvik, J., Pauza, M. E., Iiizumi, M. and Watabe, K. 2005. FAS expression inversely correlates with PTEN level in prostate cancer and a PI 3-kinase inhibitor synergizes with FAS siRNA to induce apoptosis. Oncogene 24: 5389–5395.PubMedCrossRefGoogle Scholar
  6. Bandyopadhyay, S., Zhan, R., Wang, Y., Pai, S. K., Hirota, S., Hosobe, S., Takano, Y., Saito, K., Furuta, E., Iiizumi, M., Mohinta, S., Watabe, M., Chalfant, C. and Watabe, K. 2006. Mechanism of apoptosis induced by the inhibition of fatty acid synthase in breast cancer cells. Cancer Res 66: 5934–5940.PubMedCrossRefGoogle Scholar
  7. Bang, B., Gniadecki, R. and Gajkowska, B. 2005. Disruption of lipid rafts causes apoptotic cell death in HaCaT keratinocytes. Exp Dermatol 14: 266–272.PubMedCrossRefGoogle Scholar
  8. Bauer, D. E., Hatzivassiliou, G., Zhao, F., Andreadis, C. and Thompson, C. B. 2005. ATP citrate lyase is an important component of cell growth and transformation. Oncogene 24: 6314–6322.PubMedCrossRefGoogle Scholar
  9. Berwick, D. C., Hers, I., Heesom, K. J., Moule, S. K. and Tavare, J. M. 2002. The identification of ATP-citrate lyase as a protein kinase B (Akt) substrate in primary adipocytes. J Biol Chem 277: 33895–33900.PubMedCrossRefGoogle Scholar
  10. Bonen, A., Chabowski, A., Luiken, J. J. and Glatz, J. F. 2007. Is membrane transport of FFA mediated by lipid, protein, or both? Mechanisms and regulation of protein-mediated cellular fatty acid uptake: molecular, biochemical, and physiological evidence. Physiology (Bethesda) 22: 15–29.Google Scholar
  11. Bova, G. S., Carter, B. S., Bussemakers, M. J., Emi, M., Fujiwara, Y., Kyprianou, N., Jacobs, S. C., Robinson, J. C., Epstein, J. I., Walsh, P. C. et al. 1993. Homozygous deletion and frequent allelic loss of chromosome 8p22 loci in human prostate cancer. Cancer Res 53: 3869–3873.PubMedGoogle Scholar
  12. Browne, C. D., Hindmarsh, E. J. and Smith, J. W. 2006. Inhibition of endothelial cell proliferation and angiogenesis by orlistat, a fatty acid synthase inhibitor. Faseb J 20: 2027–2035.PubMedCrossRefGoogle Scholar
  13. Brusselmans, K., De Schrijver, E., Heyns, W., Verhoeven, G. and Swinnen, J. V. 2003. Epigallocatechin-3-gallate is a potent natural inhibitor of fatty acid synthase in intact cells and selectively induces apoptosis in prostate cancer cells. Int J Cancer 106: 856–862.PubMedCrossRefGoogle Scholar
  14. Brusselmans, K., De Schrijver, E., Verhoeven, G. and Swinnen, J. V. 2005a. RNA interference-mediated silencing of the acetyl-CoA-carboxylase-alpha gene induces growth inhibition and apoptosis of prostate cancer cells. Cancer Res 65: 6719–6725.CrossRefGoogle Scholar
  15. Brusselmans, K., Vrolix, R., Verhoeven, G. and Swinnen, J. V. 2005b. Induction of cancer cell apoptosis by flavonoids is associated with their ability to inhibit fatty acid synthase activity. J Biol Chem 280: 5636–5645.CrossRefGoogle Scholar
  16. Brusselmans, K., Timmermans, L., Van de Sande, T., Van Veldhoven, P. P., Guan, G., Shechter, I., Claessens, F., Verhoeven, G. and Swinnen, J. V. 2007. Squalene synthase, a determinant of Raft-associated cholesterol and modulator of cancer cell proliferation. J Biol Chem 282: 18777–18785.PubMedCrossRefGoogle Scholar
  17. Bull, J. H., Ellison, G., Patel, A., Muir, G., Walker, M., Underwood, M., Khan, F. and Paskins, L. 2001. Identification of potential diagnostic markers of prostate cancer and prostatic intraepithelial neoplasia using cDNA microarray. Br J Cancer 84: 1512–1519.PubMedCrossRefGoogle Scholar
  18. Buzzai, M., Bauer, D. E., Jones, R. G., Deberardinis, R. J., Hatzivassiliou, G., Elstrom, R. L. and Thompson, C. B. 2005. The glucose dependence of Akt-transformed cells can be reversed by pharmacologic activation of fatty acid beta-oxidation. Oncogene 24: 4165–4173.PubMedCrossRefGoogle Scholar
  19. Chajes, V., Cambot, M., Moreau, K., Lenoir, G. M. and Joulin, V. 2006. Acetyl-CoA carboxylase alpha is essential to breast cancer cell survival. Cancer Res 66: 5287–5294.PubMedCrossRefGoogle Scholar
  20. Chalbos, D., Joyeux, C., Escot, C., Galtier, F. and Rochefort, H. 1990. Progestin-induced fatty acid synthetase in breast cancer. From molecular biology to clinical applications. Ann N Y Acad Sci 595: 67–73.PubMedCrossRefGoogle Scholar
  21. Chang, Y., Wang, J., Lu, X., Thewke, D. P. and Mason, R. J. 2005. KGF induces lipogenic genes through a PI3K and JNK/SREBP-1 pathway in H292 cells. J Lipid Res 46: 2624–2635.PubMedCrossRefGoogle Scholar
  22. Chirala, S. S., Chang, H., Matzuk, M., Abu-Elheiga, L., Mao, J., Mahon, K., Finegold, M. and Wakil, S. J. 2003. Fatty acid synthesis is essential in embryonic development: Fatty acid synthase null mutants and most of the heterozygotes die in utero. Proc Natl Acad Sci USA 100: 6358–6363.PubMedCrossRefGoogle Scholar
  23. Clegg, D. J., Wortman, M. D., Benoit, S. C., McOsker, C. C. and Seeley, R. J. 2002. Comparison of central and peripheral administration of C75 on food intake, body weight, and conditioned taste aversion. Diabetes 51: 3196–3201.PubMedCrossRefGoogle Scholar
  24. Costello, L. C. and Franklin, R. B. 1991a. Concepts of citrate production and secretion by prostate: 2. Hormonal relationships in normal and neoplastic prostate. Prostate 19: 181–205.CrossRefGoogle Scholar
  25. Costello, L. C. and Franklin, R. B. 1991b. Concepts of citrate production and secretion by prostate. 1. Metabolic relationships. Prostate 18: 25–46.CrossRefGoogle Scholar
  26. Costello, L. C. and Franklin, R. B. 1997. Citrate metabolism of normal and malignant prostate epithelial cells. Urology 50: 3–12.PubMedCrossRefGoogle Scholar
  27. Costello, L. C. and Franklin, R. B. 2005. ‘Why do tumour cells glycolyse?’: From glycolysis through citrate to lipogenesis. Mol Cell Biochem 280: 1–8.PubMedCrossRefGoogle Scholar
  28. Cui, Z., Houweling, M., Chen, M. H., Record, M., Chap, H., Vance, D. E. and Terce, F. 1996. A genetic defect in phosphatidylcholine biosynthesis triggers apoptosis in Chinese hamster ovary cells. J Biol Chem 271: 14668–14671.PubMedCrossRefGoogle Scholar
  29. De Schrijver, E., Brusselmans, K., Heyns, W., Verhoeven, G. and Swinnen, J. V. 2003. RNA interference-mediated silencing of the fatty acid synthase gene attenuates growth and induces morphological changes and apoptosis of LNCaP prostate cancer cells. Cancer Res 63: 3799–3804.PubMedGoogle Scholar
  30. De Vos, M. L., Lawrence, D. S. and Smith, C. D. 2001. Cellular pharmacology of cerulenin analogs that inhibit protein palmitoylation. Biochem Pharmacol 62: 985–995.PubMedCrossRefGoogle Scholar
  31. Demierre, M. F., Higgins, P. D., Gruber, S. B., Hawk, E. and Lippman, S. M. 2005. Statins and cancer prevention. Nat Rev Cancer 5: 930–942.PubMedCrossRefGoogle Scholar
  32. Denoyelle, C., Albanese, P., Uzan, G., Hong, L., Vannier, J. P., Soria, J. and Soria, C. 2003. Molecular mechanism of the anti-cancer activity of cerivastatin, an inhibitor of HMG-CoA reductase, on aggressive human breast cancer cells. Cell Signal 15: 327–338.PubMedCrossRefGoogle Scholar
  33. Doege, H. and Stahl, A. 2006. Protein-mediated fatty acid uptake: Novel insights from in vivo models. Physiology (Bethesda) 21: 259–268.Google Scholar
  34. 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. and Thompson, C. B. 2004. Akt stimulates aerobic glycolysis in cancer cells. Cancer Res 64: 3892–3899.PubMedCrossRefGoogle Scholar
  35. Esslimani-Sahla, M., Thezenas, S., Simony-Lafontaine, J., Kramar, A., Lavaill, R., Chalbos, D. and Rochefort, H. 2007. Increased expression of fatty acid synthase and progesterone receptor in early steps of human mammary carcinogenesis. Int J Cancer 120: 224–229.PubMedCrossRefGoogle Scholar
  36. Gabrielson, E. W., Pinn, M. L., Testa, J. R. and Kuhajda, F. P. 2001. Increased fatty acid synthase is a therapeutic target in mesothelioma. Clin Cancer Res 7: 153–157.PubMedGoogle Scholar
  37. Ginsberg, H. N. 1998. Lipoprotein physiology. Endocrinol Metab Clin North Am 27: 503–519.PubMedCrossRefGoogle Scholar
  38. Graner, E., Tang, D., Rossi, S., Baron, A., Migita, T., Weinstein, L. J., Lechpammer, M., Huesken, D., Zimmermann, J., Signoretti, S. and Loda, M. 2004. The isopeptidase USP2a regulates the stability of fatty acid synthase in prostate cancer. Cancer Cell 5: 253–261.PubMedCrossRefGoogle Scholar
  39. Hager, M. H., Solomon, K. R. and Freeman, M. R. 2006. The role of cholesterol in prostate cancer. Curr Opin Clin Nutr Metab Care 9: 379–385.PubMedCrossRefGoogle Scholar
  40. Hahn-Windgassen, A., Nogueira, V., Chen, C. C., Skeen, J. E., Sonenberg, N. and Hay, N. 2005. Akt activates the mammalian target of rapamycin by regulating cellular ATP level and AMPK activity. J Biol Chem 280: 32081–32089.PubMedCrossRefGoogle Scholar
  41. Hancock, J. F. 2006. Lipid rafts: Contentious only from simplistic standpoints. Nat Rev Mol Cell Biol 7: 456–462.PubMedCrossRefGoogle Scholar
  42. Hatzivassiliou, G., Zhao, F., Bauer, D. E., Andreadis, C., Shaw, A. N., Dhanak, D., Hingorani, S. R., Tuveson, D. A. and Thompson, C. B. 2005. ATP citrate lyase inhibition can suppress tumor cell growth. Cancer Cell 8: 311–321.PubMedCrossRefGoogle Scholar
  43. Heemers, H., Vanderhoydonc, F., Heyns, W., Verhoeven, G. and Swinnen, J. V. 2000. Progestins and androgens increase expression of Spot 14 in T47-D breast tumor cells. Biochem Biophys Res Commun 269: 209–212.PubMedCrossRefGoogle Scholar
  44. Heemers, H., Verrijdt, G., Organe, S., Claessens, F., Heyns, W., Verhoeven, G. and Swinnen, J. V. 2004. Identification of an androgen response element in intron 8 of the sterol regulatory element-binding protein cleavage-activating protein gene allowing direct regulation by the androgen receptor. J Biol Chem 279: 30880–30887.PubMedCrossRefGoogle Scholar
  45. Heemers, H. V., Verhoeven, G. and Swinnen, J. V. 2006. Androgen activation of the sterol regulatory element-binding protein pathway: Current insights. Mol Endocrinol 20: 2265–2277.PubMedCrossRefGoogle Scholar
  46. Hochachka, P. W., Rupert, J. L., Goldenberg, L., Gleave, M. and Kozlowski, P. 2002. Going malignant: The hypoxia–cancer connection in the prostate. Bioessays 24: 749–757.PubMedCrossRefGoogle Scholar
  47. Horton, J. D., Goldstein, J. L. and Brown, M. S. 2002. SREBPs: Activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest 109: 1125–1131.PubMedGoogle Scholar
  48. Inoki, K., Li, Y., Zhu, T., Wu, J. and Guan, K. L. 2002. TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat Cell Biol 4: 648–657.PubMedCrossRefGoogle Scholar
  49. Kapur, P., Rakheja, D., Roy, L. C. and Hoang, M. P. 2005. Fatty acid synthase expression in cutaneous melanocytic neoplasms. Mod Pathol 18: 1107–1112.PubMedCrossRefGoogle Scholar
  50. Khanzada, U. K., Pardo, O. E., Meier, C., Downward, J., Seckl, M. J. and Arcaro, A. 2006. Potent inhibition of small-cell lung cancer cell growth by simvastatin reveals selective functions of Ras isoforms in growth factor signalling. Oncogene 25: 877–887.PubMedCrossRefGoogle Scholar
  51. Kinlaw, W. B., Quinn, J. L., Wells, W. A., Roser-Jones, C. and Moncur, J. T. 2006. Spot 14: A marker of aggressive breast cancer and a potential therapeutic target. Endocrinology 147: 4048–4055.PubMedCrossRefGoogle Scholar
  52. Knowles, L. M. and Smith, J. W. 2007. Genome-wide changes accompanying knockdown of fatty acid synthase in breast cancer. BMC Genomics 8: 168.PubMedCrossRefGoogle Scholar
  53. Kridel, S. J., Axelrod, F., Rozenkrantz, N. and Smith, J. W. 2004. Orlistat is a novel inhibitor of fatty acid synthase with antitumor activity. Cancer Res 64: 2070–2075.PubMedCrossRefGoogle Scholar
  54. Kuhajda, F. P., Jenner, K., Wood, F. D., Hennigar, R. A., Jacobs, L. B., Dick, J. D. and Pasternack, G. R. 1994. Fatty acid synthesis: A potential selective target for antineoplastic therapy. Proc Natl Acad Sci USA 91: 6379–6383.PubMedCrossRefGoogle Scholar
  55. Kuhajda, F. P. 2000. Fatty-acid synthase and human cancer: New perspectives on its role in tumor biology. Nutrition 16: 202–208.PubMedCrossRefGoogle Scholar
  56. Kuhajda, F. P., Pizer, E. S., Li, J. N., Mani, N. S., Frehywot, G. L. and Townsend, C. A. 2000. Synthesis and antitumor activity of an inhibitor of fatty acid synthase. Proc Natl Acad Sci USA 97: 3450–3454.PubMedCrossRefGoogle Scholar
  57. Kuhajda, F. P. 2006. Fatty acid synthase and cancer: New application of an old pathway. Cancer Res 66: 5977–5980.PubMedCrossRefGoogle Scholar
  58. Kumar-Sinha, C., Ignatoski, K. W., Lippman, M. E., Ethier, S. P. and Chinnaiyan, A. M. 2003. Transcriptome analysis of HER2 reveals a molecular connection to fatty acid synthesis. Cancer Res 63: 132–139.PubMedGoogle Scholar
  59. Lawrence, D. S., Zilfou, J. T. and Smith, C. D. 1999. Structure–activity studies of cerulenin analogues as protein palmitoylation inhibitors. J Med Chem 42: 4932–4941.PubMedCrossRefGoogle Scholar
  60. Li, B. H. and Tian, W. X. 2004. Inhibitory effects of flavonoids on animal fatty acid synthase. J Biochem (Tokyo) 135: 85–91.Google Scholar
  61. Li, J. N., Mahmoud, M. A., Han, W. F., Ripple, M. and Pizer, E. S. 2000. Sterol regulatory element-binding protein-1 participates in the regulation of fatty acid synthase expression in colorectal neoplasia. Exp Cell Res 261: 159–165.PubMedCrossRefGoogle Scholar
  62. Li, J. N., Gorospe, M., Chrest, F. J., Kumaravel, T. S., Evans, M. K., Han, W. F. and Pizer, E. S. 2001. Pharmacological inhibition of fatty acid synthase activity produces both cytostatic and cytotoxic effects modulated by p53. Cancer Res 61: 1493–1499.PubMedGoogle Scholar
  63. Little, J. L., Wheeler, F. B., Fels, D. R., Koumenis, C. and Kridel, S. J. 2007. Inhibition of fatty acid synthase induces endoplasmic reticulum stress in tumor cells. Cancer Res 67: 1262–1269.PubMedCrossRefGoogle Scholar
  64. Liu, B., Wang, Y., Fillgrove, K. L. and Anderson, V. E. 2002. Triclosan inhibits enoyl-reductase of type I fatty acid synthase in vitro and is cytotoxic to MCF-7 and SKBr-3 breast cancer cells. Cancer Chemother Pharmacol 49: 187–193.PubMedCrossRefGoogle Scholar
  65. Loftus, T. M., Jaworsky, D. E., Frehywot, G. L., Townsend, C. A., Ronnett, G. V., Lane, M. D. and Kuhajda, F. P. 2000. Reduced food intake and body weight in mice treated with fatty acid synthase inhibitors. Science 288: 2379–2381.PubMedCrossRefGoogle Scholar
  66. Lu, S. and Archer, M. C. 2005. Fatty acid synthase is a potential molecular target for the chemoprevention of breast cancer. Carcinogenesis 26: 153–157.PubMedCrossRefGoogle Scholar
  67. Magnard, C., Bachelier, R., Vincent, A., Jaquinod, M., Kieffer, S., Lenoir, G. M. and Venezia, N. D. 2002. BRCA1 interacts with acetyl-CoA carboxylase through its tandem of BRCT domains. Oncogene 21: 6729–6739.PubMedCrossRefGoogle Scholar
  68. Malvoisin, E. and Wild, F. 1990. Effect of drugs which inhibit cholesterol synthesis on syncytia formation in vero cells infected with measles virus. Biochim Biophys Acta 1042: 359–364.PubMedGoogle Scholar
  69. Mathupala, S. P., Ko, Y. H. and Pedersen, P. L. 2006. Hexokinase II: cancer’s double-edged sword acting as both facilitator and gatekeeper of malignancy when bound to mitochondria. Oncogene 25: 4777–4786.PubMedCrossRefGoogle Scholar
  70. Medes, G., Thomas, A. and Weinhouse, S. 1953. Metabolism of neoplastic tissue. IV. A study of lipid synthesis in neoplastic tissue slices in vitro. Cancer Res 13: 27–29.PubMedGoogle Scholar
  71. Menendez, J. A., Mehmi, I., Atlas, E., Colomer, R. and Lupu, R. 2004a. Novel signaling molecules implicated in tumor-associated fatty acid synthase-dependent breast cancer cell proliferation and survival: Role of exogenous dietary fatty acids, p53-p21WAF1/CIP1, ERK1/2 MAPK, p27KIP1, BRCA1, and NF-kappaB. Int J Oncol 24: 591–608.Google Scholar
  72. Menendez, J. A., Mehmi, I., Verma, V. A., Teng, P. K. and Lupu, R. 2004b. Pharmacological inhibition of fatty acid synthase (FAS): A novel therapeutic approach for breast cancer chemoprevention through its ability to suppress Her-2/neu (erbB-2) oncogene-induced malignant transformation. Mol Carcinog 41: 164–178.CrossRefGoogle Scholar
  73. Menendez, J. A., Vellon, L., Mehmi, I., Oza, B. P., Ropero, S., Colomer, R. and Lupu, R. 2004c. Inhibition of fatty acid synthase (FAS) suppresses HER2/neu (erbB-2) oncogene overexpression in cancer cells. Proc Natl Acad Sci USA 101: 10715–10720.CrossRefGoogle Scholar
  74. Menendez, J. A., Vellon, L., Colomer, R. and Lupu, R. 2005a. Pharmacological and small interference RNA-mediated inhibition of breast cancer-associated fatty acid synthase (oncogenic antigen-519) synergistically enhances Taxol (paclitaxel)-induced cytotoxicity. Int J Cancer 115: 19–35.CrossRefGoogle Scholar
  75. Menendez, J. A., Vellon, L. and Lupu, R. 2005b. Antitumoral actions of the anti-obesity drug orlistat (XenicalTM) in breast cancer cells: blockade of cell cycle progression, promotion of apoptotic cell death and PEA3-mediated transcriptional repression of Her2/neu (erbB-2) oncogene. Ann Oncol 16: 1253–1267.CrossRefGoogle Scholar
  76. Middleton, E., Jr., Kandaswami, C. and Theoharides, T. C. 2000. The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacol Rev 52: 673–751.PubMedGoogle Scholar
  77. Milgraum, L. Z., Witters, L. A., Pasternack, G. R. and Kuhajda, F. P. 1997. Enzymes of the fatty acid synthesis pathway are highly expressed in in situ breast carcinoma. Clin Cancer Res 3: 2115–2120.PubMedGoogle Scholar
  78. Moncur, J. T., Park, J. P., Memoli, V. A., Mohandas, T. K. and Kinlaw, W. B. 1998. The “Spot 14” gene resides on the telomeric end of the 11q13 amplicon and is expressed in lipogenic breast cancers: implications for control of tumor metabolism. Proc Natl Acad Sci USA 95: 6989–6994.PubMedCrossRefGoogle Scholar
  79. Moore, S., Knudsen, B., True, L. D., Hawley, S., Etzioni, R., Wade, C., Gifford, D., Coleman, I. and Nelson, P. S. 2005. Loss of stearoyl-CoA desaturase expression is a frequent event in prostate carcinoma. Int J Cancer 114: 563–571.PubMedCrossRefGoogle Scholar
  80. Moreau, K., Dizin, E., Ray, H., Luquain, C., Lefai, E., Foufelle, F., Billaud, M., Lenoir, G. M. and Venezia, N. D. 2006. BRCA1 affects lipid synthesis through its interaction with acetyl-CoA carboxylase. J Biol Chem 281: 3172–3181.PubMedCrossRefGoogle Scholar
  81. Muck, A. O., Seeger, H. and Wallwiener, D. 2004. Inhibitory effect of statins on the proliferation of human breast cancer cells. Int J Clin Pharmacol Ther 42: 695–700.PubMedGoogle Scholar
  82. Mycielska, M. E., Broke-Smith, T. P., Palmer, C. P., Beckerman, R., Nastos, T., Erguler, K. and Djamgoz, M. B. 2006. Citrate enhances in vitro metastatic behaviours of PC-3M human prostate cancer cells: status of endogenous citrate and dependence on aconitase and fatty acid synthase. Int J Biochem Cell Biol 38: 1766–1777.PubMedCrossRefGoogle Scholar
  83. Ohashi, K., Osuga, J., Tozawa, R., Kitamine, T., Yagyu, H., Sekiya, M., Tomita, S., Okazaki, H., Tamura, Y., Yahagi, N., Iizuka, Y., Harada, K., Gotoda, T., Shimano, H., Yamada, N. and Ishibashi, S. 2003. Early embryonic lethality caused by targeted disruption of the 3-hydroxy-3-methylglutaryl-CoA reductase gene. J Biol Chem 278: 42936–42941.PubMedCrossRefGoogle Scholar
  84. Omura, S. 1976. The antibiotic cerulenin, a novel tool for biochemistry as an inhibitor of fatty acid synthesis. Bacteriol Rev 40: 681–697.PubMedGoogle Scholar
  85. Ookhtens, M., Kannan, R., Lyon, I. and Baker, N. 1984. Liver and adipose tissue contributions to newly formed fatty acids in an ascites tumor. Am J Physiol 247: R146–153.PubMedGoogle Scholar
  86. Osaki, M., Oshimura, M. and Ito, H. 2004. PI3K-Akt pathway: Its functions and alterations in human cancer. Apoptosis 9: 667–676.PubMedCrossRefGoogle Scholar
  87. Piyathilake, C. J., Frost, A. R., Manne, U., Bell, W. C., Weiss, H., Heimburger, D. C. and Grizzle, W. E. 2000. The expression of fatty acid synthase (FASE) is an early event in the development and progression of squamous cell carcinoma of the lung. Hum Pathol 31: 1068–1073.PubMedCrossRefGoogle Scholar
  88. Pizer, E. S., Jackisch, C., Wood, F. D., Pasternack, G. R., Davidson, N. E. and Kuhajda, F. P. 1996a. Inhibition of fatty acid synthesis induces programmed cell death in human breast cancer cells. Cancer Res 56: 2745–2747.Google Scholar
  89. Pizer, E. S., Wood, F. D., Heine, H. S., Romantsev, F. E., Pasternack, G. R. and Kuhajda, F. P. 1996b. Inhibition of fatty acid synthesis delays disease progression in a xenograft model of ovarian cancer. Cancer Res 56: 1189–1193.Google Scholar
  90. Pizer, E. S., Wood, F. D., Pasternack, G. R. and Kuhajda, F. P. 1996c. Fatty acid synthase (FAS): A target for cytotoxic antimetabolites in HL60 promyelocytic leukemia cells. Cancer Res 56: 745–751.Google Scholar
  91. Pizer, E. S., Chrest, F. J., DiGiuseppe, J. A. and Han, W. F. 1998. Pharmacological inhibitors of mammalian fatty acid synthase suppress DNA replication and induce apoptosis in tumor cell lines. Cancer Res 58: 4611–4615.PubMedGoogle Scholar
  92. Pizer, E. S., Thupari, J., Han, W. F., Pinn, M. L., Chrest, F. J., Frehywot, G. L., Townsend, C. A. and Kuhajda, F. P. 2000. Malonyl-coenzyme-A is a potential mediator of cytotoxicity induced by fatty-acid synthase inhibition in human breast cancer cells and xenografts. Cancer Res 60: 213–218.PubMedGoogle Scholar
  93. Porstmann, T., Griffiths, B., Chung, Y. L., Delpuech, O., Griffiths, J. R., Downward, J. and Schulze, A. 2005. PKB/Akt induces transcription of enzymes involved in cholesterol and fatty acid biosynthesis via activation of SREBP. Oncogene 24: 6465–6481.PubMedGoogle Scholar
  94. Prowatke, I., Devens, F., Benner, A., Grone, E. F., Mertens, D., Grone, H. J., Lichter, P. and Joos, S. 2007. Expression analysis of imbalanced genes in prostate carcinoma using tissue microarrays. Br J Cancer 96: 82–88.PubMedCrossRefGoogle Scholar
  95. Rakheja, D., Kapur, P., Hoang, M. P., Roy, L. C. and Bennett, M. J. 2005. Increased ratio of saturated to unsaturated C18 fatty acids in colonic adenocarcinoma: Implications for cryotherapy and lipid raft function. Med Hypotheses 65: 1120–1123.PubMedCrossRefGoogle Scholar
  96. Ramirez de Molina, A., Rodriguez-Gonzalez, A., Gutierrez, R., Martinez-Pineiro, L., Sanchez, J., Bonilla, F., Rosell, R. and Lacal, J. 2002. Overexpression of choline kinase is a frequent feature in human tumor-derived cell lines and in lung, prostate, and colorectal human cancers. Biochem Biophys Res Commun 296: 580–583.PubMedCrossRefGoogle Scholar
  97. Rodriguez-Gonzalez, A., Ramirez de Molina, A., Banez-Coronel, M., Megias, D. and Lacal, J. C. 2005. Inhibition of choline kinase renders a highly selective cytotoxic effect in tumour cells through a mitochondrial independent mechanism. Int J Oncol 26: 999–1008.PubMedGoogle Scholar
  98. Sabine, J. R., Abraham, S. and Chaikoff, I. L. 1967. Control of lipid metabolism in hepatomas: insensitivity of rate of fatty acid and cholesterol synthesis by mouse hepatoma BW7756 to fasting and to feedback control. Cancer Res 27: 793–799.PubMedGoogle Scholar
  99. Sato, R. and Takano, T. 1995. Regulation of intracellular cholesterol metabolism. Cell Struct Funct 20: 421–427.PubMedCrossRefGoogle Scholar
  100. Sebastiani, V., Botti, C., Di Tondo, U., Visca, P., Pizzuti, L., Santeusanio, G. and Alo, P. L. 2006. Tissue microarray analysis of FAS, Bcl-2, Bcl-x, ER, PgR, Hsp60, p53 and Her2-neu in breast carcinoma. Anticancer Res 26: 2983–2987.PubMedGoogle Scholar
  101. Sebti, S. M. 2005. Protein farnesylation: Implications for normal physiology, malignant transformation, and cancer therapy. Cancer Cell 7: 297–300.PubMedCrossRefGoogle Scholar
  102. Shah, U. S., Dhir, R., Gollin, S. M., Chandran, U. R., Lewis, D., Acquafondata, M. and Pflug, B. R. 2006. Fatty acid synthase gene overexpression and copy number gain in prostate adenocarcinoma. Hum Pathol 37: 401–409.PubMedCrossRefGoogle Scholar
  103. Shurbaji, M. S., Kalbfleisch, J. H. and Thurmond, T. S. 1996. Immunohistochemical detection of a fatty acid synthase (OA-519) as a predictor of progression of prostate cancer. Hum Pathol 27: 917–921.PubMedCrossRefGoogle Scholar
  104. Simons, K. and Ikonen, E. 1997. Functional rafts in cell membranes. Nature 387: 569–572.PubMedCrossRefGoogle Scholar
  105. Simons, K. and Toomre, D. 2000. Lipid rafts and signal transduction. Nat Rev Mol Cell Biol 1: 31–39.PubMedCrossRefGoogle Scholar
  106. Swinnen, J. V., Ulrix, W., Heyns, W. and Verhoeven, G. 1997. Coordinate regulation of lipogenic gene expression by androgens: Evidence for a cascade mechanism involving sterol regulatory element binding proteins. Proc Natl Acad Sci USA 94: 12975–12980.PubMedCrossRefGoogle Scholar
  107. Swinnen, J. V., Heemers, H., Deboel, L., Foufelle, F., Heyns, W. and Verhoeven, G. 2000a. Stimulation of tumor-associated fatty acid synthase expression by growth factor activation of the sterol regulatory element-binding protein pathway. Oncogene 19: 5173–5181.CrossRefGoogle Scholar
  108. Swinnen, J. V., Vanderhoydonc, F., Elgamal, A. A., Eelen, M., Vercaeren, I., Joniau, S., Van Poppel, H., Baert, L., Goossens, K., Heyns, W. and Verhoeven, G. 2000b. Selective activation of the fatty acid synthesis pathway in human prostate cancer. Int J Cancer 88: 176–179.CrossRefGoogle Scholar
  109. Swinnen, J. V., Roskams, T., Joniau, S., Van Poppel, H., Oyen, R., Baert, L., Heyns, W. and Verhoeven, G. 2002. Overexpression of fatty acid synthase is an early and common event in the development of prostate cancer. Int J Cancer 98: 19–22.PubMedCrossRefGoogle Scholar
  110. Swinnen, J. V., Van Veldhoven, P. P., Timmermans, L., De Schrijver, E., Brusselmans, K., Vanderhoydonc, F., Van de Sande, T., Heemers, H., Heyns, W. and Verhoeven, G. 2003. Fatty acid synthase drives the synthesis of phospholipids partitioning into detergent-resistant membrane microdomains. Biochem Biophys Res Commun 302: 898–903.PubMedCrossRefGoogle Scholar
  111. Swinnen, J. V., Heemers, H., van de Sande, T., de Schrijver, E., Brusselmans, K., Heyns, W. and Verhoeven, G. 2004. Androgens, lipogenesis and prostate cancer. J Steroid Biochem Mol Biol 92: 273–279.PubMedCrossRefGoogle Scholar
  112. Swinnen, J. V., Brusselmans, K. and Verhoeven, G. 2006. Increased lipogenesis in cancer cells: New players, novel targets. Curr Opin Clin Nutr Metab Care 9: 358–365.PubMedCrossRefGoogle Scholar
  113. Szutowicz, A., Kwiatkowski, J. and Angielski, S. 1979. Lipogenetic and glycolytic enzyme activities in carcinoma and nonmalignant diseases of the human breast. Br J Cancer 39: 681–687.PubMedGoogle Scholar
  114. Takahashi, K. A., Smart, J. L., Liu, H. and Cone, R. D. 2004. The anorexigenic fatty acid synthase inhibitor, C75, is a nonspecific neuronal activator. Endocrinology 145: 184–193.PubMedCrossRefGoogle Scholar
  115. Thupari, J. N., Pinn, M. L. and Kuhajda, F. P. 2001. Fatty acid synthase inhibition in human breast cancer cells leads to malonyl-CoA-induced inhibition of fatty acid oxidation and cytotoxicity. Biochem Biophys Res Commun 285: 217–223.PubMedCrossRefGoogle Scholar
  116. Thupari, J. N., Landree, L. E., Ronnett, G. V. and Kuhajda, F. P. 2002. C75 increases peripheral energy utilization and fatty acid oxidation in diet-induced obesity. Proc Natl Acad Sci USA 99: 9498–9502.PubMedGoogle Scholar
  117. Tozawa, R., Ishibashi, S., Osuga, J., Yagyu, H., Oka, T., Chen, Z., Ohashi, K., Perrey, S., Shionoiri, F., Yahagi, N., Harada, K., Gotoda, T., Yazaki, Y. and Yamada, N. 1999. Embryonic lethality and defective neural tube closure in mice lacking squalene synthase. J Biol Chem 274: 30843–30848.PubMedCrossRefGoogle Scholar
  118. Turyn, J., Schlichtholz, B., Dettlaff-Pokora, A., Presler, M., Goyke, E., Matuszewski, M., Kmiec, Z., Krajka, K. and Swierczynski, J. 2003. Increased activity of glycerol 3-phosphate dehydrogenase and other lipogenic enzymes in human bladder cancer. Horm Metab Res 35: 565–569.PubMedCrossRefGoogle Scholar
  119. Van de Sande, T., De Schrijver, E., Heyns, W., Verhoeven, G. and Swinnen, J. V. 2002. Role of the phosphatidylinositol 3′-kinase/PTEN/Akt kinase pathway in the overexpression of fatty acid synthase in LNCaP prostate cancer cells Cancer Res62: 642–646.PubMedGoogle Scholar
  120. Van de Sande, T., Roskams, T., Lerut, E., Joniau, S., Van Poppel, H., Verhoeven, G. and Swinnen, J. V. 2005. High-level expression of fatty acid synthase in human prostate cancer tissues is linked to activation and nuclear localization of Akt/PKB. J Pathol 206: 214–219.PubMedCrossRefGoogle Scholar
  121. van der Sanden, M. H., Houweling, M., van Golde, L. M. and Vaandrager, A. B. 2003. Inhibition of phosphatidylcholine synthesis induces expression of the endoplasmic reticulum stress and apoptosis-related protein CCAAT/enhancer-binding protein-homologous protein (CHOP/GADD153). Biochem J 369: 643–650.PubMedCrossRefGoogle Scholar
  122. Veillard, N. R. and Mach, F. 2002. Statins: The new aspirin? Cell Mol Life Sci 59: 1771–1786.PubMedCrossRefGoogle Scholar
  123. Visca, P., Sebastiani, V., Botti, C., Diodoro, M. G., Lasagni, R. P., Romagnoli, F., Brenna, A., De Joannon, B. C., Donnorso, R. P., Lombardi, G. and Alo, P. L. 2004. Fatty acid synthase (FAS) is a marker of increased risk of recurrence in lung carcinoma. Anticancer Res 24: 4169–4173.PubMedGoogle Scholar
  124. Wang, H. Q., Altomare, D. A., Skele, K. L., Poulikakos, P. I., Kuhajda, F. P., Di Cristofano, A. and Testa, J. R. 2005. Positive feedback regulation between AKT activation and fatty acid synthase expression in ovarian carcinoma cells. Oncogene 24: 3574–3582.PubMedCrossRefGoogle Scholar
  125. Wang, X. and Tian, W. 2001. Green tea epigallocatechin gallate: A natural inhibitor of fatty-acid synthase. Biochem Biophys Res Commun 288: 1200–1206.PubMedCrossRefGoogle Scholar
  126. Weiss, L., Hoffmann, G. E., Schreiber, R., Andres, H., Fuchs, E., Korber, E. and Kolb, H. J. 1986. Fatty-acid biosynthesis in man, a pathway of minor importance. Purification, optimal assay conditions, and organ distribution of fatty-acid synthase. Biol Chem Hoppe Seyler 367: 905–912.PubMedGoogle Scholar
  127. Wieman, H. L., Wofford, J. A. and Rathmell, J. C. 2007. Cytokine stimulation promotes glucose uptake via phosphatidylinositol-3 kinase/Akt regulation of Glut1 activity and trafficking. Mol Biol Cell 18: 1437–1446.PubMedCrossRefGoogle Scholar
  128. Xia, Z., Tan, M. M., Wong, W. W., Dimitroulakos, J., Minden, M. D. and Penn, L. Z. 2001. Blocking protein geranylgeranylation is essential for lovastatin-induced apoptosis of human acute myeloid leukemia cells. Leukemia 15: 1398–1407.PubMedCrossRefGoogle Scholar
  129. Yahagi, N., Shimano, H., Hasegawa, K., Ohashi, K., Matsuzaka, T., Najima, Y., Sekiya, M., Tomita, S., Okazaki, H., Tamura, Y., Iizuka, Y., Nagai, R., Ishibashi, S., Kadowaki, T., Makuuchi, M., Ohnishi, S., Osuga, J. and Yamada, N. 2005. Co-ordinate activation of lipogenic enzymes in hepatocellular carcinoma. Eur J Cancer 41: 1316–1322.PubMedCrossRefGoogle Scholar
  130. Yang, C. S., Landau, J. M., Huang, M. T. and Newmark, H. L. 2001. Inhibition of carcinogenesis by dietary polyphenolic compounds. Annu Rev Nutr 21: 381–406.PubMedCrossRefGoogle Scholar
  131. Yang, Y. A., Han, W. F., Morin, P. J., Chrest, F. J. and Pizer, E. S. 2002. Activation of fatty acid synthesis during neoplastic transformation: Role of mitogen-activated protein kinase and phosphatidylinositol 3-kinase. Exp Cell Res 279: 80–90.PubMedCrossRefGoogle Scholar
  132. Yeh, C. W., Chen, W. J., Chiang, C. T., and Lin-Shiau, S. Y. Lin, J. K. 2003. Suppression of fatty acid synthase in MCF-7 breast cancer cells by tea and tea polyphenols: A possible mechanism for their hypolipidemic effects. Pharmacogenomics J.Google Scholar
  133. Yoon, S., Lee, M. Y., Park, S. W., Moon, J. S., Koh, Y. K., Ahn, Y. H., Park, B. W. and Kim, K. S. 2007. Up-regulation of acetyl-CoA carboxylase {alpha} and fatty acid synthase by human epidermal growth factor receptor 2 at the translational level in breast cancer cells. J Biol Chem 282: 26122–26131.PubMedCrossRefGoogle Scholar
  134. Zhao, W., Kridel, S., Thorburn, A., Kooshki, M., Little, J., Hebbar, S. and Robbins, M. 2006. Fatty acid synthase: A novel target for antiglioma therapy. Br J Cancer 95: 869–878.PubMedCrossRefGoogle Scholar
  135. Zhong, W. B., Wang, C. Y., Chang, T. C. and Lee, W. S. 2003. Lovastatin induces apoptosis of anaplastic thyroid cancer cells via inhibition of protein geranylgeranylation and de novo protein synthesis. Endocrinology 144: 3852–3859.PubMedCrossRefGoogle Scholar
  136. Zhou, W., Simpson, P. J., McFadden, J. M., Townsend, C. A., Medghalchi, S. M., Vadlamudi, A., Pinn, M. L., Ronnett, G. V. and Kuhajda, F. P. 2003. Fatty acid synthase inhibition triggers apoptosis during S phase in human cancer cells. Cancer Res 63: 7330–7337.PubMedGoogle Scholar
  137. Zhou, W., Han, W. F., Landree, L. E., Thupari, J. N., Pinn, M. L., Bililign, T., Kim, E. K., Vadlamudi, A., Medghalchi, S. M., El Meskini, R., Ronnett, G. V., Townsend, C. A. and Kuhajda, F. P. 2007. Fatty acid synthase inhibition activates AMP-activated protein kinase in SKOV3 human ovarian cancer cells. Cancer Res 67: 2964–2971.PubMedCrossRefGoogle Scholar
  138. Zhuang, L., Lin, J., Lu, M. L., Solomon, K. R. and Freeman, M. R. 2002. Cholesterol-rich lipid rafts mediate akt-regulated survival in prostate cancer cells. Cancer Res 62: 2227–2231.PubMedGoogle Scholar
  139. Zhuang, L., Kim, J., Adam, R. M., Solomon, K. R. and Freeman, M. R. 2005. Cholesterol targeting alters lipid raft composition and cell survival in prostate cancer cells and xenografts. J Clin Invest 115: 959–968.PubMedGoogle Scholar

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© Springer Science + Business Media, LLC 2009

Authors and Affiliations

  1. 1.Laboratory for Experimental Medicine and EndocrinologyKatholieke Universiteit LeuvenBelgium

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