Transcriptional regulation of lipogenesis as a therapeutic target for cancer treatment

Abstract

A significant increase in lipogenesis is a metabolic hallmark of proliferating tumor cells and is required for oncogenic transformation of epithelial cells. Although most normal cells acquire the bulk of their fatty acids from the circulation, tumor cells synthesize more than 90 % of required lipids de novo. Consistent with an increased demand for lipid synthesis, diverse human cancer cells express high levels of lipogenic enzymes, such as fatty acid synthase (FASN) and stearoyl-CoA desaturase 1 (SCD1). The sterol regulatory element-binding protein 1 (SREBP1) and peroxisome proliferator-activated receptor γ (PPARγ) are master regulators of lipogenesis in diverse organisms. Previous studies have established that FASN and SCD1, the major transcriptional targets of SREBP1 and PPARγ, promote synthesis of fatty acids, which then serve as ligands for PPARγ activation. This review focuses on the potential therapeutic value of these lipogenic transcription factors as targets in cancer treatment. © Springer Science+Business Media New York 2014.