[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-384357-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-384357-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","pelp1-inhibition-by-smip34-reduces-endometrial-cancer-progression-via-attenuation-of-ribosomal-biogenesis","PELP1 inhibition by SMIP34 reduces endometrial cancer progression via attenuation of ribosomal biogenesis","","Endometrial carcinoma (ECa) is a leading cause of cancer morbidity and mortality in women, and effective targeted therapies remain insufficient. This study evaluates SMIP34, a small-molecule inhibitor of the oncogene PELP1, in established and patient-derived ECa models. SMIP34 lowers cell viability, colony formation, and induces apoptosis. Transcriptomic and mechanistic analyses show negative regulation of ribosome biogenesis and translation, with disruption of the Rix complex, reduced ribosomal biogenesis and protein synthesis, and improved response to mTOR inhibitors, including effects in organoids, explants, and ECa xenografts.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/pelp1-inhibition-by-smip34-reduces-endometrial-cancer-progression-via-attenuation-of-ribosomal-biogenesis/384357/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/pelp1-inhibition-by-smip34-reduces-endometrial-cancer-progression-via-attenuation-of-ribosomal-biogenesis/384357.png","ImageObject",300,407,{"name":42,"@type":43},"kopisore","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-29","2026-09-24",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",10,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What is SMIP34 and what target does it inhibit?","Question",{"text":63,"@type":64},"SMIP34 is a small-molecule inhibitor of PELP1. It suppresses PELP1 oncogenic signaling in endometrial cancer models.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How does SMIP34 affect endometrial cancer cells?",{"text":68,"@type":64},"SMIP34 significantly reduces cell viability and colony formation and induces apoptosis. It also decreases ribosomal biogenesis and new protein synthesis.",{"name":70,"@type":61,"acceptedAnswer":71},"Does SMIP34 work better in combination with other therapies?",{"text":72,"@type":64},"Yes. SMIP34 enhances the efficacy of mTOR inhibitors in reducing viability of endometrial cancer cells, and it reduces growth of ECa xenografts.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},384357,1790902244,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":55,"slug":125},"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":145},962090880963,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","PELP1 inhibition by SMIP34 reduces endometrial cancer progression via attenuation of ribosomal biogenesis Xue Yang 1,2, Zexuan Liu 1,3, Weiwei Tang 1,4, Uday P. Pratap 1, Alexia B. Collier 1,  \nKristin A. Altwegg 1,5, Rahul Gopalam 1, Xiaonan Li 1, Yaxia Yuan6, Daohong Zhou6, Zhao Lai7, Yidong Chen7, Gangadhara R. Sareddy 1,5, Philip T. Valente8, Edward R. Kost 1,  \nSuryavathi Viswanadhapalli 1,5  and Ratna K. Vadlamudi 1,5,9   \n1 Department of Obstetrics and Gynecology, University of Texas Health San Antonio, TX, USA  \n2 Department of Obstetrics and Gynecology, Second Xiangya Hospital, Central South University, Changsha, China  \n3 Department of Oncology, Xiangya Hospital, Central South University, Changsha, China  \n4 Department of Obstetrics and Gynecology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, China  \n5 Mays Cancer Center, University of Texas Health San Antonio, TX, USA  \n6 Department of Biochemistry & Structural Biology, University of Texas Health San Antonio, TX, USA  \n7 Department of Molecular Medicine, Department of Population Sciences, and Greehey Children’s Cancer Research Institute, University of Texas Health San Antonio, San Antonio, TX, USA  \n8 Department of Pathology, University of Texas Health San Antonio, TX, USA  \n9 Audie L. Murphy Division, South Texas Veterans Health Care System, San Antonio, TX, USA  \nKeywords  \nendometrial cancer; mTOR; PELP1; rapamycin; ribosomal biogenesis  \nCorrespondence  \nR. K. Vadlamudi and S. Viswanadhapalli, Department of Obstetrics & Gynecology, UT Health San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA  \nTel: +1 2105674912 (RKV); +1 2104503073 (SV)  \nE-mail: [vadlamudi@uthscsa.edu](vadlamudi@uthscsa.edu) (RKV); [viswanadhapa@uthscsa.edu](viswanadhapa@uthscsa.edu) (SV)  \n(Received 18 April 2023, revised 31 August 2023, accepted 4 September 2023, available online 1 November 2023)  \ndoi:10 . 1002/1878-0261 .13539  \nEndometrial carcinoma (ECa) is the fourth most common cancer among women. The oncogene PELP1 is frequently overexpressed in a variety of cancers, including ECa. We recently generated SMIP34, a small-molecule inhibitor of PELP1 that suppresses PELP1 oncogenic signaling. In this study, we assessed the effectiveness of SMIP34 in treating ECa. Treatment of established and primary patient-derived ECa cells with SMIP34 resulted in a significant reduction of cell viability, colony formation ability, and induction of apoptosis. RNA-seq analyses showed that SMIP34-regulated genes were negatively correlated with ribosome biogenesis and eukaryotic translation pathways. Mechanistic studies showed that the Rix complex, which is essential for ribosomal biogenesis, is disrupted upon SMIP34 binding to PELP1 . Biochemical assays confirmed that SMIP34 reduced ribosomal biogenesis and new protein synthesis. Further, SMIP34 enhanced the efficacy ofmTOR inhibitors in reducing viability of ECa cells. SMIP34 is also effective in reducing cell viability in ECa organoids in vitro and explants ex vivo. Importantly, SMIP34 treatment resulted in a significant reduction of the growth of ECa xenografts. Collectively, these findings underscore the potential of SMIP34 in treating ECa.  \n1. Introduction  \nIn the United States, endometrial carcinoma (ECa) is the fourth most common cancer in women and sixth most  \ncommon malignancy among women to cause death [1] . The endometrioid ECa (EEC), a subtype of ECa, which makes up about 80% of all ECa, is regulated by signaling from estrogen (E2, 17-b-estradiol) [2] . Major risk factors  \nAbbreviations  \nAKT, protein kinase B; ATCC, American Type Culture Collection; DepMap, dependency map; E2, 17-beta-estradiol; ECa, endometrial cancer; EEC, endometrioid endometrial cancer; GSEA, gene set enrichment analysis; IHC, immunohistochemistry; IP, immunoprecipitation; mTOR, mammalian target of rapamycin; OPP, O-propargyl-puromycin; PDE, patient-derived explant; PDO, patient-derived organo","cbCaitkadTCh1FE6","https://ap.wps.com/l/cbCaitkadTCh1FE6","pdf",4784783,21,"English","# Introduction\n## Background and unmet need for targeted therapy\n## Risk factors and current treatment limitations\n## Oncogenic signaling and therapeutic rationale\n## Role of PELP1 in cancer progression","[{\"question\":\"What is SMIP34 and what target does it inhibit?\",\"answer\":\"SMIP34 is a small-molecule inhibitor of PELP1. It suppresses PELP1 oncogenic signaling in endometrial cancer models.\"},{\"question\":\"How does SMIP34 affect endometrial cancer cells?\",\"answer\":\"SMIP34 significantly reduces cell viability and colony formation and induces apoptosis. It also decreases ribosomal biogenesis and new protein synthesis.\"},{\"question\":\"Does SMIP34 work better in combination with other therapies?\",\"answer\":\"Yes. SMIP34 enhances the efficacy of mTOR inhibitors in reducing viability of endometrial cancer cells, and it reduces growth of ECa xenografts.\"}]","PELP1 inhibition by SMIP34 reduces endometrial cancer progression via attenuation of ribosomal biogenesis | PDF",1790262774,53]