[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-333801-105":59,"doc-detail-333801-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","the-deubiquitinating-enzyme-usp11-regulates-breast-cancer-progression-by-stabilizing-pgam5","The deubiquitinating enzyme USP11 regulates breast cancer progression by stabilizing PGAM5","","Breast cancer is common worldwide, and phosphoglycerate mutase 5 (PGAM5) is implicated in cancer biology, yet its role in breast cancer remained unclear. This study reports high PGAM5 expression in breast tumors and demonstrates that PGAM5 controls breast cancer cell proliferation, invasion, apoptosis, and ferroptosis. USP11 overexpression increases, while USP11 knockdown decreases, breast cancer growth and metastasis both in vitro and in vivo. Mechanistically, USP11 stabilizes PGAM5 by removing ubiquitin, preventing proteasome-mediated degradation, and USP11/PGAM5 activates iron-death proteins to drive disease progression.",{"@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":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/the-deubiquitinating-enzyme-usp11-regulates-breast-cancer-progression-by-stabilizing-pgam5/333801/",{"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/the-deubiquitinating-enzyme-usp11-regulates-breast-cancer-progression-by-stabilizing-pgam5/333801.png","ImageObject",300,407,{"name":92,"@type":93},"Levi","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-01","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":24},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the main finding about USP11 in breast cancer?","Question",{"text":112,"@type":113},"USP11 regulates breast cancer progression by stabilizing PGAM5, and manipulating USP11 levels changes breast cancer growth and metastasis in vitro and in vivo.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does USP11 affect PGAM5 at the molecular level?",{"text":117,"@type":113},"USP11 deubiquitinates PGAM5, protecting it from proteasome-mediated degradation and enhancing PGAM5 stability and signaling.",{"name":119,"@type":110,"acceptedAnswer":120},"What role does ferroptosis play in the proposed mechanism?",{"text":121,"@type":113},"The USP11/PGAM5 axis promotes breast cancer progression by activating ferroptosis-related proteins, suggesting the pathway supports resistance to iron-dependent cell death.","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},333801,1790165171,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":24,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},7971461740909,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Zhang et al. Breast Cancer Research (2024) 26:135  \n[https://doi.org/10.1186/s13058-024-01892-9](https://doi.org/10.1186/s13058-024-01892-9)  \nBreast Cancer Research  \nRESEARCH Open Access  \nThe deubiquitinating enzyme USP11 regulates breast cancer progression by stabilizing PGAM5  \nNannan Zhang 1†, Quhui Wang 1†, Yunpeng Lu 1†, Feiran Wang 1 and Zhixian He 1*  \nAbstract  \nBreast cancer is common worldwide. Phosphoglycerate mutase 5 (PGAM5) belongs to the phosphoglyceratemutase family and plays an important role in many cancers. However, research on its role in breast cancer remains unclear. The present investigation highlights the significant expression of PGAM5 in breast cancer and its essential role in cell proliferation, invasion, apoptosis and the regulation of ferroptosis in breast cancer cells. Overexpression or knockdown of ubiquitin-specific protease 11 (USP11) promotes or inhibits the growth and metastasis of breast cancer cells, respectively, in vitro and in vivo. Mechanistically, USP11 stabilizes PGAM5 via de-ubiquitination, protecting it from proteasome-mediated degradation. In addition, the USP11/PGAM5 complex promotes breast cancer progression by activating iron death-related proteins, indicating that the synergy between USP11 and PGAM5 may serve as a predictor of disease outcome and provide a new treatment strategy for breast cancer.  \nKeywords PGAM5, Breast cancer, USP11, Ferroptosis  \nBackground  \nIn 2020, breast cancer emerged as the predominant form of cancer worldwide, surpassing other cancer types, according to a report by the World Health Organization (2021) [1]. To alleviate the global burden of cancer, there is an immediate necessity for the development of more cost-effective therapeutic approaches and strategies. PGAM5, a member of the phosphoglycerate mutase family, exhibits a distinctive role among its counterparts by operating as a serine/threonine protein phosphatase instead of a phosphoglycerate mutase [2]. Its involvement  \n†Nannan Zhang, Quhui Wang andYunpeng Lu contributed equally to this work.  \n*Correspondence: Zhixian He[hezhixiangs@sina.com](hezhixiangs@sina.com)  \n1Department of General Surgery, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, Jiangsu 226000, China  \nin cell apoptosis and necrosis occurs via mitochondrial damage-induced autophagy [3–5]. It has been found that the expression of PGAM5 is upregulated in many cancer types, promoting tumor progression [6–8]. Despite its widespread expression in various cancers, the function and regulatory mechanisms of PGAM5 in breast cancer remain unclear. Through bioinformatics analysis, we successfully identified high expression of PGAM5 in breast cancer. Subsequent investigations have shed further light on the crucial role of PGAM5 in various cellular processes, including proliferation, invasion, apoptosis, and ferroptosis, in breast cancer cells.  \nFerroptosis, a form of iron-dependent cell death, is characterized by lipid peroxidation. Disturbances in the cysteine/glutamate antiporter (system xc-) and antioxidant systems can result in iron overload. Mechanistically, SLC7A11, a member of the solute carrier family 7, supplies cysteine for glutathione (GSH) synthesis. Subsequently, GSH is utilized by GSH-dependent  \n© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material.","cbCaiabshNdIPbRR","https://ap.wps.com/l/cbCaiabshNdIPbRR","pdf",7667799,13,"English","# Abstract\n# Background\n## Ferroptosis and iron-dependent cell death\n## USP11 as a regulator in cancer signaling\n# Materials and methods\n## Cell culture and transfection","[{\"question\":\"What is the main finding about USP11 in breast cancer?\",\"answer\":\"USP11 regulates breast cancer progression by stabilizing PGAM5, and manipulating USP11 levels changes breast cancer growth and metastasis in vitro and in vivo.\"},{\"question\":\"How does USP11 affect PGAM5 at the molecular level?\",\"answer\":\"USP11 deubiquitinates PGAM5, protecting it from proteasome-mediated degradation and enhancing PGAM5 stability and signaling.\"},{\"question\":\"What role does ferroptosis play in the proposed mechanism?\",\"answer\":\"The USP11/PGAM5 axis promotes breast cancer progression by activating ferroptosis-related proteins, suggesting the pathway supports resistance to iron-dependent cell death.\"}]","The deubiquitinating enzyme USP11 regulates breast cancer progression by stabilizing PGAM5 | PDF",1790004175,33]