Targeting FASN in Breast Cancer and the Discovery of Promising Inhibitors from Natural Products Derived from Traditional Chinese Medicine

Figure 2

FASN related metabolic and signal transduction pathways. De novo fatty acid synthesis is an important hallmark of cancer cells, differentiating it from normal cells. Palmitate is the primary synthesized 16-carbon fatty acid, from which other lipids are also formed. FASN is the key enzyme for the synthesis of palmitate and it affects the amount of palmitate formed. The overexpression of FASN allows for the de novo synthesis of essential lipids for the formation of cell membrane and for the production of extra energy via beta-oxidation and lipid modification of proteins. The binding of the growth factor and the growth factor receptor results in the activation of their downstream PI3k-Akt and ERK1 (and ERK2) signal transduction pathway. The FASN expression is regulated by several growth factors, including epidermal growth factor receptor (EGFR), HER2, steroid hormone, and steroid hormone receptors (such as ER, PR, and AR). However, there is complicated regulation of FASN expression by these growth factors. FASN expression and growth factor-dependent signaling are coregulating.