Mo Yijun, Lin Lina, Zhang Jianhua, Yu Changhui
Department of Thoracic Surgery, Shenzhen Hospital, Southern Medical University, Shenzhen, 518110, China.
School of Nursing, Guangzhou Xinhua University, Guangzhou, 510520, China.
Biochem Cell Biol. 2022 Feb;100(1):68-74. doi: 10.1139/bcb-2021-0175. Epub 2021 Oct 20.
Sterol O-acyltransferase 1 (SOAT1) is a key enzyme in lipid metabolism, which mediates cholesterol esterification metabolism and is closely associated with many cancers. However, the role of SOAT1 in lung cancer invasion remains unclear. We found that SOAT1 expression was positively correlated with lung cancer invasion. Downregulation of SOAT1 inhibited invasion, mitochondrial fragmentation, AKT phosphorylation, and phospho-Drp (Ser616) in lung cancer cells and promoted intracellular free cholesterol accumulation. Mechanistically, the AKT phosphorylation inhibitor MK-2206 alleviated both SOAT1 overexpression and high expression-induced mitochondrial fragmentation and lung cancer cell invasion. Furthermore, intracellular free cholesterol accumulation reduced AKT phosphorylation, SREBP1 mRNA expression, cell invasion, and mitochondrial fragmentation in lung cancer cells with high SOAT1 expression. In summary, our findings suggest that SOAT1 promotes lung cancer invasion by activating the PI3K/AKT signaling pathway by downregulating intracellular free cholesterol levels, thereby affecting the regulation of mitochondrial fragmentation.
固醇O-酰基转移酶1（SOAT1）是脂质代谢中的关键酶，介导胆固醇酯化代谢，且与多种癌症密切相关。然而，SOAT1在肺癌侵袭中的作用仍不清楚。我们发现SOAT1表达与肺癌侵袭呈正相关。SOAT1的下调抑制了肺癌细胞的侵袭、线粒体碎片化、AKT磷酸化和磷酸化Drp（Ser616），并促进了细胞内游离胆固醇的积累。机制上，AKT磷酸化抑制剂MK-2206减轻了SOAT1过表达和高表达诱导的线粒体碎片化及肺癌细胞侵袭。此外，细胞内游离胆固醇的积累降低了高SOAT1表达的肺癌细胞中的AKT磷酸化、SREBP1 mRNA表达、细胞侵袭和线粒体碎片化。总之，我们的研究结果表明，SOAT1通过下调细胞内游离胆固醇水平激活PI3K/AKT信号通路，从而影响线粒体碎片化的调节，进而促进肺癌侵袭。
