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Chunk #6 — Fatty Acid Metabolism and Cancer

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Mammalian SWI/SNF Enzymes and the Epigenetics of Tumor Cell Metabolic Reprogramming.
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In tissues with high rates of lipogenesis such as liver, lactating mammary gland, and adipose tissue, the fatty acid synthesis pathway has three principal functions: storage of excess energy as fat, synthesis of lipids from carbohydrate or protein precursors when dietary lipids are scarce, and synthesis of milk fats during lactation. Most normal cells in other tissues do not synthesize fatty acids de novo but preferentially use circulating lipids. However, upregulation of both lipogenic genes and overall lipogenesis are observed widely in tumors in those non-lipogenic tissues (65). Depending on the tumor type, tumor cells synthesize up to 95% of saturated and mono-unsaturated fatty acids de novo from acetyl CoA despite a sufficient exogenous supply of fatty acids (66). Lipogenic enzymes, such as FASN, ACC, and ACLY that are required for fatty acid biosynthesis, and SREBP1, the master regulator of lipogenic gene expression, are overexpressed in many cancers, including breast (67–70). FASN is a key enzyme involved in energy storage from excess carbohydrates to fat in liver and adipose tissue, during lactation in breast, and in support of reproduction in