子宫内膜癌（EC）是一种常见的恶性肿瘤，与糖尿病、肥胖等代谢性疾病密切相关。晚期糖基化终产物（AGEs）是还原糖与生物大分子的氨基反应形成的复杂聚合物，介导许多慢性代谢疾病的发生和发展。最新研究表明，AGEs的积累可以影响肿瘤微环境、代谢和信号通路，从而影响肿瘤的恶性进展。然而，AGEs影响EC的机制尚不清楚。我们的研究旨在调查AGEs如何通过代谢途径促进EC的发展，并探索其潜在的潜在机制。我们的实验结果表明，AGEs通过晚期糖基化终产物受体（RAGE）上调胆碱激酶α（CHKA）介导的胆碱代谢，激活PI3K/AKT通路并增强EC细胞的恶性生物学行为。虚拟筛选和分子动力学模拟表明知母皂苷A3（timo A3）可以靶向CHKA抑制AGE诱导的EC进展，新发现的CHKA抑制剂可能成为治疗EC的新型靶向抑制剂。这项研究提供了新的治疗策略，为 EC 的治疗做出了贡献。© 作者 2024。由牛津大学出版社出版。版权所有。如需商业重复使用，请联系 reprints@oup.com 获取转载和转载的翻译权。所有其他权限均可通过我们网站文章页面上的“权限”链接通过我们的 RightsLink 服务获得 - 欲了解更多信息，请联系journals.permissions@oup.com。

Endometrial cancer (EC) is a common malignant tumor that is closely associated with metabolic disorders such as diabetes and obesity. Advanced glycation end products (AGEs) are complex polymers formed by the reaction of reducing sugars with the amino groups of biomacromolecules, mediating the occurrence and development of many chronic metabolic diseases. Recent research has demonstrated that the accumulation of AGEs can affect the tumor microenvironment, metabolism, and signaling pathways, thereby affecting the malignant progression of tumors. However, the mechanism by which AGEs affect EC is unclear. Our research aimed to investigate how AGEs promote the development of EC through metabolic pathways and to explore their potential underlying mechanisms. Our experimental results demonstrated that AGEs upregulated the choline metabolism mediated by choline kinase alpha (CHKA) through the receptor for advanced glycation end products (RAGE), activating the PI3K/AKT pathway and enhancing the malignant biological behavior of EC cells. Virtual screening and molecular dynamics simulation revealed that timosaponin A3 (timo A3) could target CHKA to inhibit AGE-induced progression of EC and that a newly discovered CHKA inhibitor could be a novel targeted inhibitor for the treatment of EC. This study provides new therapeutic strategies and contributes to the treatment of EC.© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.