[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-350031-105":59,"doc-detail-350031-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","glycogen-synthase-1-promotes-breast-cancer-progression-by-promoting-ib-ubiquitination-and-degradation-independent-of-its-canonical-enzyme-function","Glycogen synthase 1 promotes breast cancer progression by promoting IκBα ubiquitination and degradation independent of its canonical enzyme function","","Glycogen synthase 1 (GYS1) is upregulated in cancers and linked to therapy resistance, yet its role in breast cancer has remained unclear. This study identifies a non-canonical, glycogen-independent mechanism: Gys1 loss suppresses breast cancer cell proliferation and migration and reduces tumor growth in vivo. The effects are not reproduced by removing other glycogen synthesis enzymes or by pharmacologic GYS1 inhibition.",{"@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/glycogen-synthase-1-promotes-breast-cancer-progression-by-promoting-ib-ubiquitination-and-degradation-independent-of-its-canonical-enzyme-function/350031/",{"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/glycogen-synthase-1-promotes-breast-cancer-progression-by-promoting-ib-ubiquitination-and-degradation-independent-of-its-canonical-enzyme-function/350031.png","ImageObject",300,407,{"name":92,"@type":93},"Jake","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-23","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":8},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What role does GYS1 play in breast cancer progression according to the study?","Question",{"text":112,"@type":113},"GYS1 promotes breast cancer progression through a non-canonical mechanism that activates NF-κB signaling. It supports proliferation and migration of breast cancer cells and enhances tumor growth in vivo.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Is the oncogenic effect of GYS1 dependent on its canonical enzyme function?",{"text":117,"@type":113},"No. Neither genetic loss of other glycogen synthesis enzymes nor pharmacological inhibition of GYS1 recapitulates the same effects, showing the oncogenic role is uncoupled from its metabolic enzymatic function.",{"name":119,"@type":110,"acceptedAnswer":120},"How does GYS1 activate NF-κB signaling mechanistically?",{"text":121,"@type":113},"GYS1 promotes ubiquitination and proteasomal degradation of IκBα by stabilizing the interaction between IκBα and the E3 ubiquitin ligase BTRC. This enables NF-κB nuclear translocation.","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},350031,1790143677,{"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":8,"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},962084928904,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Zhuo et al. Cell Communication and Signaling (2026) 24:197  \n[https://doi.org/10.1186/s12964-026-02728-z](https://doi.org/10.1186/s12964-026-02728-z)  \nCell Communication and Signaling  \nRESEARCH Open Access  \nGlycogen synthase 1 promotes breast cancer  progression by promoting IκBα ubiquitination and degradation independent of its canonical enzyme function  \nShixuan Zhuo1†, Zinan Wang1†, Yu Zhang2 andYan Chen1,2*  \nAbstract  \nBreast cancer remains a global health challenge, with triple-negative breast cancer (TNBC) posing a particular therapeutic difficulty. Glycogen synthase 1 (GYS1), a key glycogen metabolic enzyme, is upregulated in various cancers under hypoxic stress and is associated with therapy resistance, but its functional role in BRCAs remains incompletely defined. Here, we identify a non-canonical, glycogen-independent mechanism by which GYS1 promotes breast cancer progression. We demonstrate that Gys1 knockout suppresses proliferation and migration of breast cancer cells in vitro and inhibits tumor growth in vivo. Crucially, neither ablation of other glycogen synthesis enzymes nor pharmacological inhibition of GYS1 recapitulates these effects, uncoupling the oncogenic role of GYS1 from its metabolic function. Mechanistically, GYS1 activates the canonical NF-κB pathway by promoting the ubiquitination and degradation of IκBα . GYS1 stabilizes the interaction between IκBα and its E3 ubiquitin ligase BTRC, facilitating IκBα proteasomal degradation and enabling nuclear translocation of NF-κB. Our findings establish GYS1 as a novel scaffold protein and an upstream regulator of NF-κB signaling independent of its enzymatic function, nominating it as a promising therapeutic target for breast cancer particularly for TNBC subtype that lacks effective treatment.  \nKeywords Breast cancer, Tumorigenesis, GYS1, Glycogen, NF-κB, IκBα, Ubiquitination  \n†Shixuan Zhuo and Zinan Wang contributed equally to this work.  \n*Correspondence: Yan Chen[ychen3@sibs.ac.cn](ychen3@sibs.ac.cn)  \n1Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China  \n2School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China  \nIntroduction  \nBreast cancer (BRCA) persists as a formidable global health challenge, maintaining its status as the most frequently diagnosed malignancy among women and ranking among the top three most common cancers worldwide [1, 2]. Over recent decades, concerted efforts in screening and therapeutic advancements have led to a consistent decline in breast cancer mortality rates in several high-income regions, including North America and the European Union. This encouraging trend is largely attributable to the widespread implementation of early detection programs and the development of increasingly effective systemic therapies [3]. Despite this progress, a  \n© The Author(s) 2026. 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. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creati](http://creati)[vecommons.org/licenses/by-nc","cbCaifomHRJmHf9O","https://ap.wps.com/l/cbCaifomHRJmHf9O","pdf",9875632,15,"English","# Abstract\n## Introduction\n## Glycogen synthase 1 and glycogen metabolism in cancer","[{\"question\":\"What role does GYS1 play in breast cancer progression according to the study?\",\"answer\":\"GYS1 promotes breast cancer progression through a non-canonical mechanism that activates NF-κB signaling. It supports proliferation and migration of breast cancer cells and enhances tumor growth in vivo.\"},{\"question\":\"Is the oncogenic effect of GYS1 dependent on its canonical enzyme function?\",\"answer\":\"No. Neither genetic loss of other glycogen synthesis enzymes nor pharmacological inhibition of GYS1 recapitulates the same effects, showing the oncogenic role is uncoupled from its metabolic enzymatic function.\"},{\"question\":\"How does GYS1 activate NF-κB signaling mechanistically?\",\"answer\":\"GYS1 promotes ubiquitination and proteasomal degradation of IκBα by stabilizing the interaction between IκBα and the E3 ubiquitin ligase BTRC. This enables NF-κB nuclear translocation.\"}]","Glycogen synthase 1 promotes breast cancer progression by promoting IκBα ubiquitination and degradation independent of its canonical enzyme function | PDF",1790086826,38]