Targeting stearoyl-CoA desaturase 1 to repress endometrial cancer progression.

Weihua Li,Huimin Bai,Keng Shen,Hongying Wu,Yanhong Tai,Jiaxin Yang,Dongyan Cao,Shiping Liu

doi:10.18632/oncotarget.24304

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.

Highlights

Endometrial carcinoma (EC) is the most common gynecologic malignancy in Europe and North America, and its incidence and mortality is gradually on the rise worldwidely
Several studies have shown that fatty acid synthase (FASN), a key lipogenic enzyme catalysing the terminal steps in the de novo biogenesis of fatty acids, and sterol regulatory elementbinding protein 1 (SREBP1) are overexpressed in endometrial cancer [23, 24]
Activation of FASN, Stearoyl-CoA desaturase 1 (SCD1) and other lipogenic genes are directly regulated by SREBP1, a major transcription factors that regulate genes involved in lipid metabolism [26, 27]

Summary

Introduction

Endometrial carcinoma (EC) is the most common gynecologic malignancy in Europe and North America, and its incidence and mortality is gradually on the rise worldwidely. In the United States, the estimated new cases and deaths from EC in 2017 are 61 380 and 10 920, respectively [1]. It is well-documented that obesity is a high risk factor for endometrial cancer. There is a linear relationship between body mass index and risk of endometrial cancer among postmenopausal women. The nature of this relationship remains to be fully elucidated [2]. Obese women have a 2~4 times greater risk of developing EC compared to women of normal weight, regardless of menopausal status [3,4,5]

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Results

Conclusion