Exogenous lipids promote the growth of breast cancer cells via CD36.

Cancer cells present sustained de novo fatty acid (FA) synthesis with increased production of saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs). This change in FA metabolism is associated with overexpression of stearoyl-CoA desaturase 1 (SCD1), which catalyses the transformation of SFAs into MUFAs (e.g., oleic acid). In this study, we provide new evidence that SCD1 inhibition leads to the anti-proliferation effect of breast cancer cells through induction of apoptosis, cell cycle arrest and migration prevention. However, the antitumor effect of the SCD1 inhibitor can be reversed by exogenous oleic acid. We hypothesize that, in addition to de novo synthesis, cancer cells may uptake exogenous FAs actively. CD36, also known as FA translocase (FAT), that functions as a transmembrane protein and mediates the uptake of FAs, is observed to be highly expressed in breast cancer tissues. Furthermore, the anti-proliferation effect caused by the SCD1 inhibitor can not be reversed by exogenous oleic acid supplementation in CD36 knockdown breast cancer cells. Our study revealed that the lipid metabolism of breast cancer is regulated not only by de novo lipogenesis but also by the availability of lipids outside cancer cells. Consistent with FA synthesis, FA uptake and transport will be another important target pathway for anticancer therapy, and the FA channel protein CD36 may provide a promising therapeutic target. Lipogenesis combined with FA transport will be a new orientation for antitumor therapy.