Fatty Acid Metabolism in Oncogenesis

Proliferatively active cells require fatty acids for functions such as membrane generation, protein modification, and bioenergetic requirements. These fatty acids are derived either from dietary sources or are synthesized by the cell. While most non-transformed cells rely on dietary-derived fatty acids to meet their biosynthetic and bioenergetic needs, many cancer cells exhibit a lipogenic phenotype with the upregulation of many of the proteins involved in de novo fatty acid synthesis. In particular, overexpression of the multi-enzyme complex fatty acid synthase (FASN) is common to many tumor cells and is often associated with poor prognosis1. In addition to increased FASN activity, oncogenic progression is often associated with the increased activity and expression of many enzymes involved in fatty acid synthesis such as acetyl-CoA carboxylase (ACC) and ATP citrate lyase (ACL)1,2.

1. Menedez, J. A. and Lupu, R. Fatty Acid Synthase and the Lipogenic Phenotype in Cancer Pathogenesis. Nature Rev. Cancer, 7, 763-777 (2007).
2. Mashima, T. et al. De Novo Fatty-Acid Synthesis and Related Pathways as Molecular Targets for Cancer Therapy. Br. J. Cancer, 100, 1369-1372 (2009).