Targeting stearoyl-CoA desaturase 1 to repress endometrial cancer progression

Abstract

// Weihua Li 1, 2 , Huimin Bai 2 , Shiping Liu 3 , Dongyan Cao 1 , Hongying Wu 4 , Keng Shen 1 , Yanhong Tai 5, * and Jiaxin Yang 1, * 1 Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Wangfujing, Beijing 100730, China 2 Department of Obstetrics and Gynecology, Beijing Chao-Yang Hospital Affiliated to Capital Medical University, Beijing 100020, China 3 Departments of Obstetrics and Gynecology, Peking University First Hospital, Beijing 100034, China 4 Institute of Radiation Medicine, The Chinese Academy of Medical Sciences, Tianjin 300192, China 5 Department of Pathology, The Affiliated Hospital of Military Medical Science Academy of Chinese People’s Liberation Army (307 Hospital of Chinese People’s Liberation Army), Beijing 100071, China * These authors contributed equally to this work Correspondence to: Yanhong Tai, email: taiyanhong29@163.com Jiaxin Yang, email: yangjiaxin007@126.com Keywords: stearoyl-CoA desaturase; endometrial cancer; therapeutic target; cell growth; cell death Received: July 28, 2017      Accepted: December 26, 2017      Published: January 24, 2018 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.