Estrogen inhibits autophagy and promotes growth of endometrial cancer by promoting glutamine metabolism

Cell Communication and Signaling

Wen-Jie Zhou¹  Ai-Jun Zhang¹  Jiang-Nan Wu²  Jie Zhang³  Yan Zhuang³  Yin-Yan He³  Jiang-Dong Xiang³  Li Yao⁴  Feng Xie⁴  Yan Wang⁴  Ke Wu⁵  Hui-Li Yang⁵  Ming-Qing Li⁵ 

[1] Center of Reproductive Medicine of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine;Clinical Epidemiology, Hospital of Obstetrics and Gynecology, Fudan University;Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine;Insititue of Obstetrics and Gynecology, Hospital of Obstetrics and Gynecology, Fudan University;NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Hospital of Obstetrics and Gynecology, Fudan University;

关键词: Uterine endometrial cancer;    CB-839;    Estrogen;    Autophagy;    Glutamine;   

DOI  :  10.1186/s12964-019-0412-9

来源: DOAJ

【 摘 要 】

Abstract Background Excessive estrogen exposure is an important pathogenic factor in uterine endometrial cancer (UEC). Recent studies have reported the metabolic properties can influence the progression of UEC. However, the underlying mechanisms have not been fully elucidated. Methods Glutaminase (GLS), MYC and autophagy levels were detected. The biological functions of estrogen-MYC-GLS in UEC cells (UECC) were investigated both in vivo and in vitro. Results Our study showed that estrogen remarkably increased GLS level through up-regulating c-Myc, and enhanced glutamine (Gln) metabolism in estrogen-sensitive UEC cell (UECC), whereas fulvestrant (an ER inhibitor antagonist) could reverse these effects. Estrogen remarkably promoted cell viability and inhibited autophagy of estrogen sensitive UECC. However, CB-839, a potent selective oral bioavailable inhibitor of both splice variants of GLS, negatively regulated Gln metabolism, and inhibited the effects of Gln and estrogen on UECC’s growth and autophagy in vitro and / or in vivo. Conclusions CB-839 triggers autophagy and restricts growth of UEC by suppressing ER/Gln metabolism, which provides new insights into the potential value of CB-839 in clinical treatment of estrogen-related UEC.

【 授权许可】

Unknown