Progesterone inhibits endometrial cancer growth by inhibiting glutamine metabolism through ASCT2

• Published in: Bioscience reports Vol. 44; no. 3; p. 1
• Main Authors: Guo, Jinqiu, Fan, Jianhui, Zhang, Yaru, Li, Mengyue, Jin, Zeen, Shang, Yuhong, Zhang, Hongshuo, Kong, Ying
• Format: Journal Article
• Language: English
• Published: England Portland Press Ltd The Biochemical Society 01.03.2024; Portland Press Ltd
• Subjects: Amino acids; Antibodies; Anticancer properties; Cancer; Cell growth; Cell Line, Tumor; Cell Proliferation - genetics; Diabetes; Endometrial cancer; Endometrial Neoplasms - drug therapy; Endometrium; Estrogens; Female; Female reproductive system; Females; Fertility; Gene Expression & Regulation; Glutamine; Glutamine - metabolism; Humans; In vivo methods and tests; Insulin; Insulin-like growth factors; Malignancy; Metabolic disorders; Metabolism; Molecular Interactions; Phenotypes; Progesterone; Progesterone - pharmacology; Reproductive system; Tumors; Uterine cancer; Xenotransplantation; Beijing China; China; Japan; Progesterone; ASCT2; Endometrial carcinoma; Glutamine metabolism
• ISSN: 0144-8463; 1573-4935
• DOI: 10.1042/BSR20232035

Endometrial carcinoma (EC) is a common malignancy that originates from the endometrium and grows in the female reproductive system. Surgeries, as current treatments for cancer, however, cannot meet the fertility needs of young women patients. Thus, progesterone (P4) therapy is indispensable due to its effective temporary preservation of female fertility. Many cancer cells are often accompanied by changes in metabolic phenotypes, and abnormally dependent on the amino acid glutamine. However, whether P4 exerts an effect on EC via glutamine metabolism is unknown. In the present study, we found that P4 could inhibit glutamine metabolism in EC cells and down-regulate the expression of the glutamine transporter ASCT2. This regulation of ASCT2 affects the uptake of glutamine. Furthermore, the in vivo xenograft studies showed that P4 inhibited tumor growth and the expression of key enzymes involved in glutamine metabolism. Our study demonstrated that the direct regulation of glutamine metabolism by P4 and its anticancer effect was mediated through the inhibition of ASCT2. These results provide a mechanism underlying the effects of P4 therapy on EC from the perspective of glutamine metabolism.