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It describes classical nuclear ERα and ERβ alongside membrane-associated GPER/GPCR pathways, explaining how ligand-bound receptors regulate proliferation, differentiation, migration, and apoptosis. The review highlights how selective ERα splicing produces isoforms (e.g., ERα66, ERα46, ERα36) and how post-translational modifications alter localization and ligand affinity, potentially reshaping ERα activity in a tissue-specific manner.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/progress-of-estrogen-receptor-and-spliceosome-in-endometrial-carcinoma-review/370891/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/progress-of-estrogen-receptor-and-spliceosome-in-endometrial-carcinoma-review/370891.png","ImageObject",300,407,{"name":92,"@type":93},"4398046744996","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-27","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the central focus of this review on endometrial carcinoma?","Question",{"text":112,"@type":113},"The review focuses on the roles of estrogen receptor signaling and estrogen receptor splicing isoforms in endometrial carcinoma, including how these processes may influence tumor development and progression.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which estrogen-related receptors are discussed in relation to EC?",{"text":117,"@type":113},"It discusses classical nuclear estrogen receptors ERα and ERβ and also the membrane-associated estrogen receptor pathway involving GPER (and related non-genomic signaling).",{"name":119,"@type":110,"acceptedAnswer":120},"How do ER splicing isoforms and post-translational modifications relate to EC biology?",{"text":121,"@type":113},"Selective splicing can generate multiple ERα proteins with different structures and functional domains, while post-translational modifications can change cellular localization and ligand affinity; together they may alter ERα signaling in a tissue-specific way and influence EC-related processes.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},370891,1790217824,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":66,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":133,"file_id":134,"file_url":135,"file_type":136,"file_size":137,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":44,"language":138,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":139,"faqs":140,"seo_title":141,"seo_description":67,"update_tm":142,"read_time":143},4398046744996,"TYPE Review  \nPUBLISHED 25 August 2025  \nDOI 10.3389/fendo.2025.1586191  \nOPEN ACCESS  \nEDITED BY  \nEva Surmacz,  \nSenior Advisor, Allysta Pharmaceuticals, Inc., United States  \nREVIEWED BY  \nHao Wang,  \nShenzhen University General Hospital, China Ilaria Cuccu,  \nSapienza University of Rome, Italy Lovlesh Thakur,  \nCleveland State University, United States  \n*CORRESPONDENCE  \nXin Li  \n [1441003313@qq.com](1441003313@qq.com)[ ](1441003313@qq.com)Jian Chen  \n [chenjian@glmc.edu.cn](chenjian@glmc.edu.cn)  \nRECEIVED 02 March 2025  \nACCEPTED 04 August 2025  \nPUBLISHED 25 August 2025  \nCITATION  \nHong Z, Mo T, Zhou P, Chen J and Li X (2025) Progress of estrogen receptor and spliceosome in endometrial carcinoma. Front. Endocrinol. 16:1586191 .  \ndoi: 10.3389/fendo.2025.1586191  \nCOPYRIGHT  \n© 2025 Hong, Mo, Zhou, Chen and Li. This isan open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nProgress of estrogen receptor and spliceosome in endometrial carcinoma  \nZiqi Hong 1, Ting Mo 1, Peiquan Zhou 2, Jian Chen 1* and Xin Li 1*  \n1Guangxi Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin, China, 2 Department of Neurosurgery, Affiliated Hospital of Guilin Medical University, Guilin, China  \nEndometrial cancer (EC) is one of the most common gynecological cancers in developed countries. Like EC, most female reproductive tract malignancies are thought to be hormonally driven, with estrogen signaling acting as an oncogenic signal. The actions of estrogen are mediated through the classical nuclear estrogen receptors a (ER-a) and b (ER-b) as well as transmembrane G proteincoupled estrogen receptors (GPR30 and GPER) . Ligand-bound estrogen receptor (ER) and GPER trigger multiple downstream signaling pathways that regulate the cell cycle, differentiation, migration, and apoptosis in various tissues, including the endometrium. Additionally, growing evidence suggests that selective splicing events at the receptor result in multiple ERa proteins with different molecular weights and functional structural domains. Examples include ER-a66, ER-a46, and ER-a36. In addition, various post-translational modifications (PTMs) further affect ER-a cellular localization and ligand affinity, resulting in a change in the cellular function. These splice isoforms and PTMs are differentially expressed in a tissue-specific manner. They mediate some aspects of ER-a signaling and may even antagonize full-length ER-a. Therefore, both ERa and its splice isoforms may play a role in the development of EC. In this review, we examine the influential roles of ER-a and ER-b, as well as the GPER estrogen signaling pathway, in EC. Our goal is to provide theoretical support for further research on the molecular mechanisms between ER and EC and to generate new ideas for the early diagnosis of EC and the development of new drugs.  \nKEYWORDS  \nestrogen, estrogen receptor, isoform, endometrial cancer, molecular mechanism  \n1 Introduction  \n1.1 Background and epidemiology of endometrial cancer  \nEndometrial cancer (EC) is a malignant tumor that originates in the glandular epithelium of the endometrium. It is the most common cancer of the female reproductive tract. The population is growing rapidly worldwide, especially in Europe and the United States (1) . Not only the occurrence of EC associated with excessive estrogen  \nFrontiers in Endocrinology 01 [frontiersin.org](frontiersin.org)  \nsecretion but also its major risk factor is the prolonged and unbalanced exposure of the endometrial glandular epithelium to estrogen. Based on histopathologic features, t","cbCaioKlwOXTfAlT","https://ap.wps.com/l/cbCaioKlwOXTfAlT","pdf",967627,"English","# Introduction\n## Background and epidemiology of endometrial cancer\n## Background introduction of estrogen receptor\n### Estrogen signaling in normal endometrium","[{\"question\":\"What is the central focus of this review on endometrial carcinoma?\",\"answer\":\"The review focuses on the roles of estrogen receptor signaling and estrogen receptor splicing isoforms in endometrial carcinoma, including how these processes may influence tumor development and progression.\"},{\"question\":\"Which estrogen-related receptors are discussed in relation to EC?\",\"answer\":\"It discusses classical nuclear estrogen receptors ERα and ERβ and also the membrane-associated estrogen receptor pathway involving GPER (and related non-genomic signaling).\"},{\"question\":\"How do ER splicing isoforms and post-translational modifications relate to EC biology?\",\"answer\":\"Selective splicing can generate multiple ERα proteins with different structures and functional domains, while post-translational modifications can change cellular localization and ligand affinity; together they may alter ERα signaling in a tissue-specific way and influence EC-related processes.\"}]","Progress of estrogen receptor and spliceosome in endometrial carcinoma - review | PDF",1790190770,23]