College of Pharmacy, Yeungnam University, Gyeongsan, Korea.
Research Institute of Cell Culture, Yeungnam University, Gyeongsan, Korea.
Mol Oncol. 2021 Feb;15(2):657-678. doi: 10.1002/1878-0261.12860. Epub 2020 Dec 5.
Leptin, a hormone predominantly derived from adipose tissue, is well known to induce growth of breast cancer cells. However, its underlying mechanisms remain unclear. In this study, we examined the role of reprogramming of lipid metabolism and autophagy in leptin-induced growth of breast cancer cells. Herein, leptin induced significant increase in fatty acid oxidation-dependent ATP production in estrogen receptor-positive breast cancer cells. Furthermore, leptin induced both free fatty acid release and intracellular lipid accumulation, indicating a multifaceted effect of leptin in fatty acid metabolism. These findings were further validated in an MCF-7 tumor xenograft mouse model. Importantly, all the aforementioned metabolic effects of leptin were mediated via autophagy activation. In addition, SREBP-1 induction driven by autophagy and fatty acid synthase induction, which is mediated by SREBP-1, plays crucial roles in leptin-stimulated metabolic reprogramming and are required for growth of breast cancer cell, suggesting a pivotal contribution of fatty acid metabolic reprogramming to tumor growth by leptin. Taken together, these results highlighted a crucial role of autophagy in leptin-induced cancer cell-specific metabolism, which is mediated, at least in part, via SREBP-1 induction.
瘦素，一种主要来源于脂肪组织的激素，众所周知能诱导乳腺癌细胞生长。然而，其潜在机制尚不清楚。在这项研究中，我们研究了脂质代谢和自噬重编程在瘦素诱导的乳腺癌细胞生长中的作用。在此，瘦素诱导雌激素受体阳性乳腺癌细胞中脂肪酸氧化依赖性 ATP 生成显著增加。此外，瘦素诱导游离脂肪酸释放和细胞内脂质积累，表明瘦素在脂肪酸代谢中具有多方面的作用。这些发现进一步在 MCF-7 肿瘤异种移植小鼠模型中得到验证。重要的是，瘦素的所有上述代谢作用都是通过自噬激活介导的。此外，自噬和脂肪酸合酶诱导 SREBP-1 的诱导，由 SREBP-1 介导，在瘦素刺激的代谢重编程中发挥关键作用，并且是乳腺癌细胞生长所必需的，这表明脂肪酸代谢重编程在瘦素诱导的肿瘤生长中起着至关重要的作用。综上所述，这些结果强调了自噬在瘦素诱导的癌细胞特异性代谢中的关键作用，这种作用至少部分是通过 SREBP-1 诱导介导的。
