Therefore, supra-physiological cytosolic accumulation of the FASN substrate malonyl-CoA, a key metabolite in the regulation of energy homeostasis,57 rather than depletion of the FASN end-product palmitate, may provide a molecular bridge linking FASN-dependent endogenous fatty acid metabolism, the MEK1/2 → ERK1/2 signaling pathway, and ERα activity in breast cancer cells. This evidence concerns the gene MAPK3 and breast cancer.