{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T22:35:15Z","timestamp":1791758115499,"version":"4.3.4"},"reference-count":44,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T00:00:00Z","timestamp":1740787200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82472719"],"award-info":[{"award-number":["82472719"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Aberrant iron metabolism is frequently observed in cancers, including endometrial cancer (EC). However, the role of transferrin receptor (TFRC), a key regulator of iron metabolism, remains unclear in endometrial cancer. We found transferrin receptor expression was significantly upregulated in endometrial cancer tissues compared to adjacent nontumor tissues, and high transferrin receptor levels were associated with poor prognosis. Functional studies revealed that transferrin receptor knockdown impaired endometrial cancer cell proliferation in\u00a0vitro and in\u00a0vivo, while transferrin receptor overexpression enhanced endometrial cancer cell proliferation. Mechanistically, transferrin receptor activated the PI3K\/AKT\/mTOR signaling pathway, as its knockdown suppressed the pathway, and rapamycin, an mTOR inhibitor, reversed transferrin receptor\u2010induced pathway activation and proliferation. Modulation of the labile iron pool by ferric ammonium citrate (FAC) or deferoxamine (DFO) rescued transferrin receptor\u2010induced biological effects. Additionally, AURKA was identified as a regulator of transferrin receptor expression. These findings demonstrate the oncogenic role of transferrin receptor in endometrial cancer and suggest that targeting iron homeostasis and the PI3K\/AKT\/mTOR pathway may represent potential therapeutic strategies for endometrial cancer.<\/jats:p>","DOI":"10.1111\/cas.70015","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T16:56:32Z","timestamp":1741712192000},"page":"1352-1365","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Transferrin Receptor Promotes Endometrial Cancer Proliferation by Activating the Iron\u2010Dependent PI3K\/AKT\/mTOR Signaling Pathway"],"prefix":"10.1111","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-0926-186X","authenticated-orcid":false,"given":"Yufei","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Clinical Medicine Qingdao University  Qingdao China"},{"name":"Department of Obstetrics and Gynecology The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Ning","sequence":"additional","affiliation":[{"name":"Center of Tumor Immunology and Cytotherapy, Medical Research Center The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine Qingdao University  Qingdao China"},{"name":"Department of Obstetrics and Gynecology The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyan","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine Qingdao University  Qingdao China"},{"name":"Department of Obstetrics and Gynecology The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Lei","sequence":"additional","affiliation":[{"name":"Center of Tumor Immunology and Cytotherapy, Medical Research Center The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhumei","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9061900"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-38474-6_4"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/jjco\/hyac011"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2011.09.007"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3322\/CA.2007.0010"},{"issue":"1","key":"e_1_2_10_7_1","first-page":"89","article-title":"\"Risk of Endometrial Cancer in Relation to Use of Oestrogen Combined With Cyclic Progestagen Therapy in Postmenopausal Women\" by S.A.A. 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