Cigarette smoke promote the tumor progression via FASN in bladder cancer and rewiring the fatty acid metabolism

Cigarette smoke has been demonstrated to stimulate the growth of existing bladder tumors by enhancing the survival and proliferation of cancer cells through the action of carcinogens present in smoke. Concurrently, Fatty Acid Synthase (FASN), a key enzyme in fatty acid synthesis crucial for lipid metabolism, exhibits dysregulation in various cancer types, often correlating with aggressive phenotypes. In this study, we reveal altered fatty acid metabolism and elevated FASN and fatty acid levels, specifically in current smokers with bladder cancer (BLCA). Notably, increased FASN levels under smoke exposure are attributed to epigenetic alterations affecting fatty acid metabolism. Cells exposed to cigarette smoke demonstrate a metabolic shift in utilizing glutamine as a carbon source and producing fatty acids. The genetic and pharmacological inhibition of FASN effectively reduces tumor growth in a CAM model exposed to smoke. FASN inhibitors like TVB 2640, currently in phase II clinical trialsclinical trials in various cancer types, may be effective for smokers with BLCA exhibiting high FASN levels. In general, FASN inhibition offers therapeutic promise for mitigating the impact of cigarette smoke on bladder cancer progression. Overall design: UMUC3 cells were treated with cigarette smoke media (10%) for 3 days (B7), or air exposed (B6). The chromatin was immunoprecipitated with acK130-H2A antibodies, followed by sequencing (ChIP-seq).