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Increased lipogenesis is critical for self-renewal and growth of breast cancer stem cells: Impact of omega-3 fatty acids
STEM CELLS ( IF 4.0 ) Pub Date : 2021-09-06 , DOI: 10.1002/stem.3452 Haiqing Luo 1, 2 , Chih-Yu Chen 2 , Xiangyong Li 2, 3 , Xin Zhang 4 , Chien-Wen Su 5 , Yinghua Liu 2 , Tinglan Cao 2 , Lei Hao 2 , Meng Wang 6 , Jing X Kang 2
STEM CELLS ( IF 4.0 ) Pub Date : 2021-09-06 , DOI: 10.1002/stem.3452 Haiqing Luo 1, 2 , Chih-Yu Chen 2 , Xiangyong Li 2, 3 , Xin Zhang 4 , Chien-Wen Su 5 , Yinghua Liu 2 , Tinglan Cao 2 , Lei Hao 2 , Meng Wang 6 , Jing X Kang 2
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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.
中文翻译：
增加脂肪生成对乳腺癌干细胞的自我更新和生长至关重要：omega-3 脂肪酸的影响
脂质代谢异常最近被认为是恶性肿瘤的新标志，但乳腺癌干细胞 (BCSC) 中脂肪酸代谢的特征以及针对该途径的潜在干预措施仍有待解决。在这里，通过使用体外 BCSC 模型、乳腺球衍生的 MCF-7 细胞和 HMLE-Twist-ER 细胞，我们发现具有干细胞样特性的细胞与它们的细胞相比表现出非常明显的脂肪酸代谢特征。亲代癌细胞，其特征是脂肪生成增加，尤其是负责产生单不饱和脂肪酸的硬脂酰辅酶A去饱和酶 1 (SCD1) 的活性，以及增强 omega-6 花生四烯酸 (AA) 的合成和利用。酶抑制剂或小干扰 RNA (siRNA) 敲除对 SCD1 活性的抑制显着限制了 BCSC 的自我更新和生长，表明 SCD1 在 BCSC 增殖中的关键作用。此外，相对于来自同一患者的非癌组织，在人类乳腺癌组织中观察到 SCD1 和其他脂肪生成酶水平升高，并且与病理分级相关。有趣的是，用 omega-3 脂肪酸、二十碳五烯酸和二十二碳六烯酸处理 BCSC，有效地下调了脂肪生成酶的表达，并显着抑制了 BCSC 的自我更新和生长。向携带 BCSC 衍生肿瘤的裸鼠添加 omega-3 脂肪酸的膳食补充剂也显着降低了它们的肿瘤负荷。
更新日期：2021-09-06
中文翻译：
增加脂肪生成对乳腺癌干细胞的自我更新和生长至关重要：omega-3 脂肪酸的影响
脂质代谢异常最近被认为是恶性肿瘤的新标志，但乳腺癌干细胞 (BCSC) 中脂肪酸代谢的特征以及针对该途径的潜在干预措施仍有待解决。在这里，通过使用体外 BCSC 模型、乳腺球衍生的 MCF-7 细胞和 HMLE-Twist-ER 细胞，我们发现具有干细胞样特性的细胞与它们的细胞相比表现出非常明显的脂肪酸代谢特征。亲代癌细胞，其特征是脂肪生成增加，尤其是负责产生单不饱和脂肪酸的硬脂酰辅酶A去饱和酶 1 (SCD1) 的活性，以及增强 omega-6 花生四烯酸 (AA) 的合成和利用。酶抑制剂或小干扰 RNA (siRNA) 敲除对 SCD1 活性的抑制显着限制了 BCSC 的自我更新和生长，表明 SCD1 在 BCSC 增殖中的关键作用。此外，相对于来自同一患者的非癌组织，在人类乳腺癌组织中观察到 SCD1 和其他脂肪生成酶水平升高，并且与病理分级相关。有趣的是，用 omega-3 脂肪酸、二十碳五烯酸和二十二碳六烯酸处理 BCSC，有效地下调了脂肪生成酶的表达，并显着抑制了 BCSC 的自我更新和生长。向携带 BCSC 衍生肿瘤的裸鼠添加 omega-3 脂肪酸的膳食补充剂也显着降低了它们的肿瘤负荷。
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