The Effects of Histone Deacetylase (HDAC) Inhibitors on FASN Intracellular Localization in Cancer Cells


  • Elizabeth Colvin University of Florida
  • Daiqing Liao The University of Florida



Fatty acid synthase, FASN, Histone deacetylase inhibitors, HDACi, Cancer


Understanding mechanisms underlying cancer biology is crucial for discovering novel and effective therapies to improve patient outcome. Increased lipid production is a major metabolic feature in cancer. The fatty acid synthase (FASN) is a key enzyme for lipid synthesis and is upregulated in cancer. Although fatty acid synthesis is generally thought to take place in the cytoplasm, it has been reported that this enzyme also localizes to the nucleus in cancer cells. We hypothesize that the intracellular localization FASN could be a potential target to decrease lipid synthesis and ultimately halt cell proliferation. Protein acetylation has been shown to regulate protein intracellular localization. We aim to assess the impact histone deacetylase inhibitors (HDACi) have on the intracellular location of FASN with the goal of reducing de novo lipid production and cancer cell proliferation. We have examined intracellular localization of FASN in cells using immunofluorescence microscopy in cancer cells treated with HDACi and did not detect obvious HDACi-induced changes in FASN localization. FASN is also regulated by other mechanisms such as phosphorylation. Future studies will examine effects of kinase inhibitors on FASN intracellular localization.

Author Biographies

Elizabeth Colvin, University of Florida

Undergraduate Student

Daiqing Liao, The University of Florida

Associate Professor in the Department of Anatomy and Cell Biology


Chakravarty, B., Gu, Z., Chirala, S. S., Wakil, S. J., & Quiocho, F. A. (2004). Human fatty acid synthase: structure and substrate selectivity of the thioesterase domain. Proc Natl Acad Sci U S A, 101(44), 15567-15572.

Chemical, C. MS-275. from

Damaskos, C., Garmpis, N., Valsami, S., Kontos, M., Spartalis, E., Kalampokas, T., et al. (2017). Histone Deacetylase Inhibitors: An Attractive Therapeutic Strategy Against Breast Cancer. Anticancer Res, 37(1), 35-46.

di Bari, M. G., Ciuffini, L., Mingardi, M., Testi, R., Soddu, S., & Barilà, D. (2006). c-Abl acetylation by histone acetyltransferases regulates its nuclear-cytoplasmic localization. EMBO Rep, 7(7), 727-733.

Flavin, R., Peluso, S., Nguyen, P. L., & Loda, M. (2010). Fatty acid synthase as a potential therapeutic target in cancer. Future Oncol, 6(4), 551-562.

Fu, X., Liang, C., Li, F., Wang, L., Wu, X., Lu, A., et al. (2018). The Rules and Functions of Nucleocytoplasmic Shuttling Proteins. Int J Mol Sci, 19(5).

Grininger, M. (2014). Perspectives on the evolution, assembly and conformational dynamics of fatty acid synthase type I (FAS I) systems. Curr Opin Struct Biol, 25, 49-56.

Liao, D., Roush, W. R., & Stowe, R. L. SR-4370. from

Lin, H. P., Cheng, Z. L., He, R. Y., Song, L., Tian, M. X., Zhou, L. S., et al. (2016). Destabilization of Fatty Acid Synthase by Acetylation Inhibits De Novo Lipogenesis and Tumor Cell Growth. Cancer Res, 76(23), 6924-6936.

Madigan, A. A., Rycyna, K. J., Parwani, A. V., Datiri, Y. J., Basudan, A. M., Sobek, K. M., et al. (2014). Novel nuclear localization of fatty acid synthase correlates with prostate cancer aggressiveness. Am J Pathol, 184(8), 2156-2162.

Maier, T., Leibundgut, M., & Ban, N. (2008). The crystal structure of a mammalian fatty acid synthase. Science, 321(5894), 1315-1322.

Röhrig, F., & Schulze, A. (2016). The multifaceted roles of fatty acid synthesis in cancer. Nat Rev Cancer, 16(11), 732-749.

Suraweera, A., O'Byrne, K. J., & Richard, D. J. (2018). Combination Therapy With Histone Deacetylase Inhibitors (HDACi) for the Treatment of Cancer: Achieving the Full Therapeutic Potential of HDACi. Front Oncol, 8, 92.

Syndax. Entinostat. from