Targeting stearoyl-CoA desaturase 1 to repress endometrial cancer progression

Oncotarget. 2018 Jan 24;9(15):12064-12078. doi: 10.18632/oncotarget.24304. eCollection 2018 Feb 23.

Abstract

Stearoyl-CoA desaturase 1 (SCD1) is an established molecular target in many primary tumors including breast, lung, pancreatic, colon and hepatocellular carcinomas. However, its potential role in supporting endometrial cancer growth and progression has not yet been determined. In this study, we evaluated the value of SCD1 as a candidate therapeutic target in human endometrial cancer. Compared with secretory and post-menopausal endometrium, SCD1 was highly expressed in normal endometrium of proliferative phase, endometrial hyperplasia and endometrial carcinoma, while was absent or low expression in non-malignant control stromal cells and adjacent normal endometrium. Knockdown of SCD1 significantly repressed endometrial cancer cell growth and induced cell apoptosis. Both short hairpin RNA targeted knockdown and chemical inhibitor of SCD1 suppressed the foci formation of AN3CA, a metastatic endometrial cell line. Xenograft model further demonstrated that reduced SCD1 expression impaired endometrial cancer growth in vivo. Taken together, these findings indicate that SCD1 is a potentially therapeutic target in human endometrial cancer. Inhibiting lipid metabolism in cancer cells would be a promising strategy for anti-cancer therapy.

Keywords: cell death; cell growth; endometrial cancer; stearoyl-CoA desaturase; therapeutic target.