2. Academic Validation
  3. Estrogen inhibits autophagy and promotes growth of endometrial cancer by promoting glutamine metabolism

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

  • Cell Commun Signal. 2019 Aug 20;17(1):99. doi: 10.1186/s12964-019-0412-9.
Wen-Jie Zhou 1 2,  Jie Zhang 3,  Hui-Li Yang 2,  Ke Wu 2,  Feng Xie 4,  Jiang-Nan Wu 5,  Yan Wang 4,  Li Yao 4,  Yan Zhuang 3,  Jiang-Dong Xiang 3,  Ai-Jun Zhang 6,  Yin-Yan He 7,  Ming-Qing Li 8 9 10
Affiliations

Affiliations

  • 1 Center of Reproductive Medicine of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No.197, Ruijin 2nd Road, Shanghai, 200025, People's Republic of China.
  • 2 NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Hospital of Obstetrics and Gynecology, Fudan University, No.1326, Pingliang Road, Shanghai, 200080, People's Republic of China.
  • 3 Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No.100, Haining Road, Shanghai, 200080, People's Republic of China.
  • 4 Insititue of Obstetrics and Gynecology, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai, 200032, People's Republic of China.
  • 5 Clinical Epidemiology, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai, 200011, People's Republic of China.
  • 6 Center of Reproductive Medicine of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No.197, Ruijin 2nd Road, Shanghai, 200025, People's Republic of China. [email protected].
  • 7 Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No.100, Haining Road, Shanghai, 200080, People's Republic of China. [email protected].
  • 8 NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Hospital of Obstetrics and Gynecology, Fudan University, No.1326, Pingliang Road, Shanghai, 200080, People's Republic of China. [email protected].
  • 9 Insititue of Obstetrics and Gynecology, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai, 200032, People's Republic of China. [email protected].
  • 10 Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai, 200011, People's Republic of China. [email protected].
PMID: 31429768 DOI: 10.1186/s12964-019-0412-9
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.

Keywords

Autophagy; CB-839; Estrogen; Glutamine; Uterine endometrial cancer.

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