Fatty acid synthase plays a role in cancer metabolism beyond providing fatty acids for phospholipid synthesis or sustaining elevations in glycolytic activity

• Fatty acid synthase (FASN) is over-expressed in cancer but its function is unknown.
• We compare utilization of fatty acids produced by FASN to those derived exogenously.
• Cancer cells do not have a specific requirement for fatty acids produced by FASN.
• Fatty acids produced by FASN are in excess of cell requirements and are excreted.
• Increased FASN activity is not required to sustain elevations in glycolysis.

Fatty acid synthase is over-expressed in many cancers and its activity is required for cancer cell survival, but the role of endogenously synthesized fatty acids in cancer is unknown. It has been suggested that endogenous fatty acid synthesis is either needed to support the growth of rapidly dividing cells, or to maintain elevated glycolysis (the Warburg effect) that is characteristic of cancer cells. Here, we investigate both hypotheses. First, we compared utilization of fatty acids synthesized endogenously from 14C-labeled acetate to those supplied exogenously as 14C-labeled palmitate in the culture medium in human breast cancer (MCF-7 and MDA-MB-231) and untransformed breast epithelial cells (MCF-10A). We found that cancer cells do not produce fatty acids that are different from those derived from exogenous palmitate, that these fatty acids are esterified to the same lipid and phospholi