Increased Lipogenesis Is Critical for Self ‐Renewal and Growth of Breast Cancer Stem Cells: Impact of Omega‐3 Fatty Acids

Breast cancer stem cells (CSC) have a distinct fatty acid profile due to the aberrant expressions of lipogenic enzymes (eg, FAS, SCD1, and FADS1/2), which are highly involved in sustaining their self-renewal, and proliferative capabilities. Omega-3 PUFA can effectively suppress the self-renewal and growth of breast CSC by downregulation of the lipogenic enzymes, especially SCD1. AbstractAberrant lipid metabolism has recently been recognized as a new hallmark of malignancy, but the characteristics of fatty acid metabolism in breast cancer stem cells (BCSC) and potential interventions targeting this pathway remain to be addressed. Here, by using thein vitro BCSC models, mammosphere-derived MCF-7 cells and HMLE-Twist-ER cells, we found that the cells with stem cell-like properties exhibited a very distinct profile of fatty acid metabolism compared with that of their parental cancer cells, characterized by increased lipogenesis, especially the activity of stearoyl-CoA desaturase 1 (SCD1) responsible for the production of monounsaturated fatty acids (MUFA), and augmented synthesis and utilization of the omega-6 arachidonic acid (AA). Suppression of SCD1 activity by either enzyme inhibitors or siRNA knockdown strikingly limited self-renewal and growth of the BCSC, suggesting a key role for SCD1 in BCSC proliferation. Furthermore, elevated levels of SCD1 and other lipogenic enzymes were observed in human breast cancer tissues relative to the non-cancer tissues from the same patients...
Source: Stem Cells - Category: Stem Cells Authors: Tags: Cancer Stem Cells Source Type: research