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Gene Review

FASN  -  fatty acid synthase

Homo sapiens

Synonyms: FAS, Fatty acid synthase, OA-519, SDR27X1
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Disease relevance of FASN


Psychiatry related information on FASN

  • apolipoprotein-E dependent role for the FAS receptor in early onset Alzheimer's disease: finding of a positive association for a polymorphism in the TNFRSF6 gene [3].
  • Those in the SHPT group had significantly impaired performance in 3 of 14 cognitive tests (Digit span forward, Stroop test part 1 and 2, and Word association test (FAS)) as compared with the controls, and also had a significantly higher depression score at the Beck Depression Inventory (BDI) (items 1-13) [4].
  • Energy deficit suppressed the resting metabolic rate and general locomotor activity and increased the activity of fatty acid synthetase (FAS) [5].
  • CONCLUSION: Significantly more fathers of children with FAS were referred for alcohol treatment, received alcohol treatment, experienced injuries, and had delirium tremens than control fathers [6].

High impact information on FASN


Chemical compound and disease context of FASN


Biological context of FASN

  • To date, elevated FASN expression in prostate cancer has not been correlated with gene copy number alterations [1].
  • This previously unrecognized ability of OA to directly affect the expression of a cluster of interrelated human cancer genes (i.e., HER2, FASN and PEA3) should open a new line of research aimed to explore the anti-cancer effects of OA [17].
  • Similarly, p185(HER2) expression was dramatically down-regulated when FAS gene expression was silenced by using the highly sequence-specific mechanism of RNA interference (RNAi) [2].
  • Furthermore, supplementation of the culture medium with palmitate or with the antioxidant vitamin E resulted in the complete rescue of cells from both ACCalpha and FAS siRNA-induced apoptosis [18].
  • Expression of a small interfering RNA (siRNA)-resistant form of ACCalpha mRNA prevented the effect of ACCalpha-RNAi but failed to prevent the effect of FAS gene silencing [18].

Anatomical context of FASN


Associations of FASN with chemical compounds

  • Pharmacological FAS inhibitors cerulenin and C75 were found to suppress p185(HER2) oncoprotein expression and tyrosine-kinase activity in breast and ovarian HER2 overexpressors [2].
  • We show that specific silencing of either the ACCalpha or the fatty acid synthase (FAS) genes in cancer cells results in a major decrease in palmitic acid synthesis [18].
  • In contrast, dietary 18:1(n-9), i.e. triolein, had no inhibitory influence on the expression of SREBP-1 or FAS [22].
  • In this study we further investigated the role of malonyl-CoA during FAS inhibition [11].
  • Interestingly, we recently established that both pharmacological inhibition of FAS activity and silencing of FAS gene expression specifically suppress Her-2/neu oncoprotein expression and tyrosine-kinase activity in breast and ovarian Her-2/neu overexpressors [23].

Physical interactions of FASN

  • Moreover, in transient transfection studies EGF stimulates the transcriptional activity of a 178 bp FAS promoter fragment harboring a complex SREBP-binding site [24].
  • To our knowledge this ACC/FAS coupled scintillation proximity assay is the only assay format that is compatible with high-throughput screening for systematic search of inhibitors against mammalian ACC [25].
  • Considerable differences existed between the specific activities of the fatty-acid synthase complex measured in human and rat lipogenic organs [26].

Enzymatic interactions of FASN


Regulatory relationships of FASN

  • Deletion or mutation of this binding site abolishes these effects and ectopic expression of dominant negative SREBP-1 inhibits FAS expression and induction in intact LNCaP cells [24].
  • Theanaphthoquinone inhibits fatty acid synthase expression in EGF-stimulated human breast cancer cells via the regulation of EGFR/ErbB-2 signaling [12].
  • The EGF-induced expression of FAS was inhibited by green and black tea extracts [28].
  • Fatty acid synthase inhibition triggers apoptosis during S phase in human cancer cells [29].
  • We evaluated the effects of FAS inhibition on E2- and TAM-induced estrogen receptor (ER) transcriptional activity by using transient cotransfection assays with an estrogen-response element reporter construct (ERE-Luciferase) [30].
  • Our results suggest that FASN and activated AKT pathway may be a potential target for therapeutic intervention for the treatment of PTC [31].

Other interactions of FASN

  • The PUFA-dependent decrease in nuclear content of mature SREBP-1 was paralleled by a 70-90% suppression in FAS gene transcription [22].
  • In summary, our findings suggest that TNQ modulates FAS expression by the regulation of EGFR/ErbB-2 pathways and induces cell death in breast cancer cells [12].
  • Unexpectedly, the specific inhibition of the de novo fatty acid synthesis with the small-molecule inhibitor of FAS activity C75 resulted in a dramatic dose-dependent enhancement (up to 500% increase) of VEGF secretion in Her-2/neu-overexpressing SK-Br3, BT-474, and SKOV3 cancer cells [23].
  • Concurrently, FAS blockade drastically activated MAPK and promoted further a prominent accumulation of HIF-1alpha in Her-2/neu overexpressors [23].
  • Liver X receptor (LXR) activation by T0901317 increased gene expression of SREBP-1c, SREBP-1a, FAS and acetyl-CoA carboxylase without altering SREBP-2 [19].

Analytical, diagnostic and therapeutic context of FASN


  1. Fatty acid synthase gene overexpression and copy number gain in prostate adenocarcinoma. Shah, U.S., Dhir, R., Gollin, S.M., Chandran, U.R., Lewis, D., Acquafondata, M., Pflug, B.R. Hum. Pathol. (2006) [Pubmed]
  2. Inhibition of fatty acid synthase (FAS) suppresses HER2/neu (erbB-2) oncogene overexpression in cancer cells. Menendez, J.A., Vellon, L., Mehmi, I., Oza, B.P., Ropero, S., Colomer, R., Lupu, R. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  3. apolipoprotein-E dependent role for the FAS receptor in early onset Alzheimer's disease: finding of a positive association for a polymorphism in the TNFRSF6 gene. Feuk, L., Prince, J.A., Breen, G., Emahazion, T., Carothers, A., St Clair, D., Brookes, A.J. Hum. Genet. (2000) [Pubmed]
  4. Neuropsychological function in relation to serum parathyroid hormone and serum 25-hydroxyvitamin D levels : The Tromsø study. Jorde, R., Waterloo, K., Saleh, F., Haug, E., Svartberg, J. J. Neurol. (2006) [Pubmed]
  5. Recovery from energy deficit in golden hamsters. Borer, K.T., Allen, E.R., Smalley, R.E., Lundell, L., Stockton, J. Am. J. Physiol. (1985) [Pubmed]
  6. Characteristics of fathers who have children with fetal alcohol syndrome or incomplete fetal alcohol syndrome. Kvigne, V.L., Leondardson, G.R., Welty, T.K. South Dakota medicine : the journal of the South Dakota State Medical Association. (2006) [Pubmed]
  7. Modular organization of genes required for complex polyketide biosynthesis. Donadio, S., Staver, M.J., McAlpine, J.B., Swanson, S.J., Katz, L. Science (1991) [Pubmed]
  8. T helper type 1/T helper type 2 cytokines and T cell death: preventive effect of interleukin 12 on activation-induced and CD95 (FAS/APO-1)-mediated apoptosis of CD4+ T cells from human immunodeficiency virus-infected persons. Estaquier, J., Idziorek, T., Zou, W., Emilie, D., Farber, C.M., Bourez, J.M., Ameisen, J.C. J. Exp. Med. (1995) [Pubmed]
  9. Food for thought: endocannabinoid modulation of lipogenesis. Lichtman, A.H., Cravatt, B.F. J. Clin. Invest. (2005) [Pubmed]
  10. Expression of the progestin-induced fatty acid synthetase in benign mastopathies and breast cancer as measured by RNA in situ hybridization. Chalbos, D., Escot, C., Joyeux, C., Tissot-Carayon, M.J., Pages, A., Rochefort, H. J. Natl. Cancer Inst. (1990) [Pubmed]
  11. Fatty acid synthase inhibition in human breast cancer cells leads to malonyl-CoA-induced inhibition of fatty acid oxidation and cytotoxicity. Thupari, J.N., Pinn, M.L., Kuhajda, F.P. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  12. Theanaphthoquinone inhibits fatty acid synthase expression in EGF-stimulated human breast cancer cells via the regulation of EGFR/ErbB-2 signaling. Weng, M.S., Ho, C.T., Ho, Y.S., Lin, J.K. Toxicol. Appl. Pharmacol. (2007) [Pubmed]
  13. A novel missense substitution (Val1483Ile) in the fatty acid synthase gene (FAS) is associated with percentage of body fat and substrate oxidation rates in nondiabetic Pima Indians. Kovacs, P., Harper, I., Hanson, R.L., Infante, A.M., Bogardus, C., Tataranni, P.A., Baier, L.J. Diabetes (2004) [Pubmed]
  14. Regulation of fatty acid synthase expression in breast cancer by sterol regulatory element binding protein-1c. Yang, Y.A., Morin, P.J., Han, W.F., Chen, T., Bornman, D.M., Gabrielson, E.W., Pizer, E.S. Exp. Cell Res. (2003) [Pubmed]
  15. Inhibition of tumor-associated fatty acid synthase activity enhances vinorelbine (Navelbine)-induced cytotoxicity and apoptotic cell death in human breast cancer cells. Menendez, J.A., Colomer, R., Lupu, R. Oncol. Rep. (2004) [Pubmed]
  16. Tamoxifen-induced anorexia is associated with fatty acid synthase inhibition in the ventromedial nucleus of the hypothalamus and accumulation of malonyl-CoA. López, M., Lelliott, C.J., Tovar, S., Kimber, W., Gallego, R., Virtue, S., Blount, M., Vázquez, M.J., Finer, N., Powles, T.J., O'Rahilly, S., Saha, A.K., Diéguez, C., Vidal-Puig, A.J. Diabetes (2006) [Pubmed]
  17. Mediterranean dietary traditions for the molecular treatment of human cancer: anti-oncogenic actions of the main olive oil's monounsaturated fatty acid oleic acid (18:1n-9). Menendez, J.A., Lupu, R. Current pharmaceutical biotechnology (2006) [Pubmed]
  18. Acetyl-CoA carboxylase alpha is essential to breast cancer cell survival. Chajès, V., Cambot, M., Moreau, K., Lenoir, G.M., Joulin, V. Cancer Res. (2006) [Pubmed]
  19. Polyunsaturated fatty acids decrease the expression of sterol regulatory element-binding protein-1 in CaCo-2 cells: effect on fatty acid synthesis and triacylglycerol transport. Field, F.J., Born, E., Murthy, S., Mathur, S.N. Biochem. J. (2002) [Pubmed]
  20. In support of fatty acid synthase (FAS) as a metabolic oncogene: extracellular acidosis acts in an epigenetic fashion activating FAS gene expression in cancer cells. Menendez, J.A., Decker, J.P., Lupu, R. J. Cell. Biochem. (2005) [Pubmed]
  21. Mapping of FASN and ACACA on two chicken microchromosomes disrupts the human 17q syntenic group well conserved in mammals. Pitel, F., Fillon, V., Heimel, C., Le Fur, N., el Khadir-Mounier, C., Douaire, M., Gellin, J., Vignal, A. Mamm. Genome (1998) [Pubmed]
  22. Sterol regulatory element binding protein-1 expression is suppressed by dietary polyunsaturated fatty acids. A mechanism for the coordinate suppression of lipogenic genes by polyunsaturated fats. Xu, J., Nakamura, M.T., Cho, H.P., Clarke, S.D. J. Biol. Chem. (1999) [Pubmed]
  23. Does endogenous fatty acid metabolism allow cancer cells to sense hypoxia and mediate hypoxic vasodilatation? Characterization of a novel molecular connection between fatty acid synthase (FAS) and hypoxia-inducible factor-1alpha (HIF-1alpha)-related expression of vascular endothelial growth factor (VEGF) in cancer cells overexpressing her-2/neu oncogene. Menendez, J.A., Vellon, L., Oza, B.P., Lupu, R. J. Cell. Biochem. (2005) [Pubmed]
  24. Stimulation of tumor-associated fatty acid synthase expression by growth factor activation of the sterol regulatory element-binding protein pathway. Swinnen, J.V., Heemers, H., Deboel, L., Foufelle, F., Heyns, W., Verhoeven, G. Oncogene (2000) [Pubmed]
  25. A homogeneous scintillation proximity assay for acetyl coenzyme A carboxylase coupled to fatty acid synthase. Seethala, R., Ma, Z., Golla, R., Cheng, D. Anal. Biochem. (2006) [Pubmed]
  26. Fatty-acid biosynthesis in man, a pathway of minor importance. Purification, optimal assay conditions, and organ distribution of fatty-acid synthase. Weiss, L., Hoffmann, G.E., Schreiber, R., Andres, H., Fuchs, E., Körber, E., Kolb, H.J. Biol. Chem. Hoppe-Seyler (1986) [Pubmed]
  27. Enzymatic reduction of phenylglyoxal and 2,3-butanedione, two commonly used arginine-modifying reagents, by the ketoacyl reductase domain of fatty acid synthase. Poulose, A.J., Kolattukudy, P.E. Int. J. Biochem. (1986) [Pubmed]
  28. Suppression of fatty acid synthase in MCF-7 breast cancer cells by tea and tea polyphenols: a possible mechanism for their hypolipidemic effects. Yeh, C.W., Chen, W.J., Chiang, C.T., Lin-Shiau, S.Y., Lin, J.K. Pharmacogenomics J. (2003) [Pubmed]
  29. Fatty acid synthase inhibition triggers apoptosis during S phase in human cancer cells. Zhou, W., Simpson, P.J., McFadden, J.M., Townsend, C.A., Medghalchi, S.M., Vadlamudi, A., Pinn, M.L., Ronnett, G.V., Kuhajda, F.P. Cancer Res. (2003) [Pubmed]
  30. Inhibition of tumor-associated fatty acid synthase activity antagonizes estradiol- and tamoxifen-induced agonist transactivation of estrogen receptor (ER) in human endometrial adenocarcinoma cells. Menendez, J.A., Oza, B.P., Atlas, E., Verma, V.A., Mehmi, I., Lupu, R. Oncogene (2004) [Pubmed]
  31. Fatty acid synthase and AKT pathway signaling in a subset of papillary thyroid cancers. Uddin, S., Siraj, A.K., Al-Rasheed, M., Ahmed, M., Bu, R., Myers, J.N., Al-Nuaim, A., Al-Sobhi, S., Al-Dayel, F., Bavi, P., Hussain, A.R., Al-Kuraya, K.S. J. Clin. Endocrinol. Metab. (2008) [Pubmed]
  32. Quaternary structure of human fatty acid synthase by electron cryomicroscopy. Brink, J., Ludtke, S.J., Yang, C.Y., Gu, Z.W., Wakil, S.J., Chiu, W. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  33. Human fatty acid synthase: properties and molecular cloning. Jayakumar, A., Tai, M.H., Huang, W.Y., al-Feel, W., Hsu, M., Abu-Elheiga, L., Chirala, S.S., Wakil, S.J. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  34. Mechanism of apoptosis induced by the inhibition of fatty acid synthase in breast cancer cells. 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., Watabe, K. Cancer Res. (2006) [Pubmed]
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