Tumor-suppressive SQLE reprograms metabolic flux: Convergence of aerobic glycolysis and cholesterol pathways in ovarian cancer
Squalene epoxidase (SQLE) exerts anti-ovarian cancer (OC) role, but its mechanistic basis remains to be defined. Through integrated bioinformatic analysis and immunohistochemistry, SQLE protein expression was found highly expressed in OC tissue compared to normal ovarian tissue, however, using the stable/transient SQLE knockdown and overexpression OC cell models, the cell proliferation and metabolism assays revealed SQLE knockdown enhanced, while SQLE overexpression suppressed cell proliferation, total/free cholesterol level, glycolytic flux and hexokinase Ⅱ (HK2) expression. SQLE positively regulated farnesyl-diphosphate farnesyltransferase 1 (FDFT1) expression. These results showed SQLE reprogramed cellular cholesterol homeostasis and aerobic glycolytic metabolism, and exerted tumor-suppressive effects in OC cells, providing a new insight for OC treatment.