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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.<\/jats:p>","DOI":"10.1042\/bsr20232035","type":"journal-article","created":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T10:30:36Z","timestamp":1709116236000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Progesterone inhibits endometrial cancer growth by inhibiting glutamine metabolism through ASCT2"],"prefix":"10.1042","volume":"44","author":[{"given":"Jinqiu","family":"Guo","sequence":"first","affiliation":[{"name":"1Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhui","family":"Fan","sequence":"additional","affiliation":[{"name":"1Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaru","family":"Zhang","sequence":"additional","affiliation":[{"name":"1Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyue","family":"Li","sequence":"additional","affiliation":[{"name":"1Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeen","family":"Jin","sequence":"additional","affiliation":[{"name":"1Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhong","family":"Shang","sequence":"additional","affiliation":[{"name":"2Department of Gynecology, First Affiliated Hospital of Dalian Medical University, Dalian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7898-755X","authenticated-orcid":false,"given":"Hongshuo","family":"Zhang","sequence":"additional","affiliation":[{"name":"3Advanced Institute for Medical Sciences, Dalian Medical University, Dalian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Kong","sequence":"additional","affiliation":[{"name":"1Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2024,3,12]]},"reference":[{"key":"2024031206563791900_B1","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1111\/1471-0528.14007","article-title":"Endometrial carcinoma-related genetic factors: application to research and clinical practice in China","volume":"123","author":"Zhou","year":"2016","journal-title":"BJOG"},{"key":"2024031206563791900_B2","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.soncn.2019.02.002","article-title":"Endometrial cancer: an overview of pathophysiology, management, and care","volume":"35","author":"Passarello","year":"2019","journal-title":"Semin. 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