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.