Open AccessIncreased lipogenesis is critical for self‐renewal and growth of breast cancer stem cells: Impact of omega‐3 fatty acids
Author(s) -
Luo Haiqing,
Chen ChihYu,
Li Xiangyong,
Zhang Xin,
Su ChienWen,
Liu Yinghua,
Cao Tinglan,
Hao Lei,
Wang Meng,
Kang Jing X.
Publication year - 2021
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.3452
Subject(s) - lipogenesis , biology , fatty acid synthesis , docosahexaenoic acid , fatty acid synthase , lipid metabolism , eicosapentaenoic acid , stem cell , fatty acid , gene knockdown , cell growth , biochemistry , microbiology and biotechnology , polyunsaturated fatty acid , apoptosis
Aberrant 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 the in 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, and augmented synthesis and utilization of the omega‐6 arachidonic acid (AA). Suppression of SCD1 activity by either enzyme inhibitors or small interfering RNA (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 noncancer tissues from the same patients and correlated with the pathological grades. Interestingly, treatment of BCSC with omega‐3 fatty acids, eicosapentaenoic acid and docosahexaenoic acid, effectively downregulated the expression of the lipogenic enzymes and markedly suppressed BCSC self‐renewal and growth. Dietary supplementation of nude mice bearing BCSC‐derived tumors with omega‐3 fatty acids also significantly reduced their tumor load. These findings have demonstrated that increased lipogenesis is critical for self‐renewal and growth of BCSC, and that omega‐3 fatty acids are effective in targeting this pathway to exert their anticancer effect.