Cancer cells are strongly dependent on alterations in specific metabolic pathways. Together with the Warburg effect, enhanced lipid biosynthesis plays a crucial role in the production of energy and metabolic intermediates, leading to uncontrolled proliferation of cancer cells. Stearoyl-CoA desaturase 1 (SCD1) is a rate-limiting enzyme of de novo lipid synthesis that catalyzes the biosynthesis of mono-unsaturated fatty acids (MUFAs) by introducing a double bond in the cis-Δ9 position of saturated fatty acids (SFAs). MUFAs, such as palmitoleic acid and oleic acid, are indispensable for the synthesis of cell membranes, the production of signaling compounds, and the generation of energy. In this study, we identified that SCD1 is highly expressed in epithelial ovarian cancer (EOC) cells compared to normal ovarian surface epithelial (NOSE) cells. Inhibition of SCD1 reduced cell proliferation and induced apoptotic cell death in ovarian cancer cells. However, it had no significant effect on the viability of NOSE cells and peripheral blood mononuclear cells (PBMCs), indicating the selective cytotoxicity against ovarian cancer cells. Furthermore, suppression of SCD1 induced endoplasmic reticulum (ER) stress by activating PERK, IRE1α, GRP78, ATF4, and CHOP in ovarian cancer cells. Addition of exogenous oleic acid rescued ER stress-mediated apoptosis caused by SCD1 suppression, highlighting the importance of lipid desaturation for cancer cell survival. Taken together, our findings suggest that SCD1 could be a potential biomarker as well as a novel therapeutic target for ovarian cancer.
【 预 览 】
附件列表
Files
Size
Format
View
Inhibition of Stearoyl-CoA Desaturase 1 (SCD1) induces ER stress-mediated apoptosis in ovarian cancer cells
PDF
download
878987797
028-85220240
