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

Abstract

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.