[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-333546-105":59,"doc-detail-333546-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","atxn3-functions-as-a-tumor-suppressor-through-potentiating-galectin-9-mediated-apoptosis-in-human-colon-adenocarcinoma","ATXN3 functions as a tumor suppressor through potentiating galectin-9-mediated apoptosis in human colon adenocarcinoma","","Research article examines how deubiquitinase ATXN3 influences colon adenocarcinoma, addressing its previously unclear function in this cancer type. Findings show ATXN3 deletion increases tumor growth in vitro and in xenograft models, whereas ATXN3 interacts with and inhibits Galectin-9 ubiquitination, lowering Galectin-9 protein and reducing Galectin-9-driven apoptosis. Ectopic Galectin-9 expression reverses ATXN3-null growth in mice. Human samples show reduced ATXN3 and Galectin-9 and a positive correlation between them.",{"@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/atxn3-functions-as-a-tumor-suppressor-through-potentiating-galectin-9-mediated-apoptosis-in-human-colon-adenocarcinoma/333546/",{"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/atxn3-functions-as-a-tumor-suppressor-through-potentiating-galectin-9-mediated-apoptosis-in-human-colon-adenocarcinoma/333546.png","ImageObject",300,407,{"name":92,"@type":93},"Maeve","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the main finding about ATXN3 in colon adenocarcinoma?","Question",{"text":112,"@type":113},"ATXN3 acts as a tumor suppressor by promoting Galectin-9–mediated apoptosis in colon cancer.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does deleting ATXN3 affect colon cancer growth?",{"text":117,"@type":113},"CRISPR-mediated ATXN3 deletion unexpectedly intensifies colon cancer growth in vitro and in xenograft models.",{"name":119,"@type":110,"acceptedAnswer":120},"What mechanism connects ATXN3 to Galectin-9?",{"text":121,"@type":113},"ATXN3 functions as a deubiquitinase that specifically targets Galectin-9, inhibiting its ubiquitination and lowering Galectin-9 protein levels.","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},333546,1790085411,{"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":34,"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},5909877438554,"https://ap-avatar.wpscdn.com/avatar/5600025385ad2bf12a7?_k=1778553567797529272","RESEARCH ARTICLE  \nATXN3 functions as a tumor suppressor through potentiatinggalectin-9-mediated apoptosis in human colon adenocarcinoma  \nReceived for publication, March 11, 2024, and in revised form, April 30, 2024 Published, Papers in Press, May 28, 2024, [https://doi.org/10.1016/j.jbc.2024.107415](https://doi.org/10.1016/j.jbc.2024.107415)  \nYang Cheng 1, Shengnan Wang 1, Qiong Gao 1, and Deyu Fang 1,2,3, *  \nFrom the 1Department of Pathology, 2Robert H. Lurie Comprehensive Cancer Center, and 3Center for Human Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA  \nReviewed by members of the JBC Editorial Board. Edited by Paul Shapiro  \nWhile deubiquitinase ATXN3 has been implicated as a potential oncogene in various types of human cancers, its role in colon adenocarcinoma remains understudied. Surprisingly, our findings demonstrate that ATXN3 exerts an antitumor effect inhuman colon cancers through potentiating Galectin-9-induced apoptosis. CRISPR-mediated ATXN3 deletion unexpectedly intensified colon cancer growth both in vitro and in xenograft colon cancers. At the molecular level, we identified ATXN3 as a bona fide deubiquitinase specifically targeting Galectin-9, as ATXN3 interacted with and inhibited Galectin-9 ubiquitination. Consequently, targeted ATXN3 ablation resulted in reduced Galectin-9 protein expression, thereby diminishing Galectin-9-induced colon cancer apoptosis and cell growth arrest. The ectopic expression of Galectin-9 fully reversed the growth of ATXN3-null colon cancer in mice. Furthermore, immunohistochemistry staining revealed a significant reduction in both ATXN3 and Galectin-9 protein expression, along with a positive correlation between them in human colon cancer. Our study identifies the first Galectin-9-specific deubiquitinase and unveils a tumor-suppressive role of ATXN3 inhuman colon cancer.  \nColon adenocarcinoma (COAD) stands as the predominant pathological variant within colon cancer, ranking as the second most prevalent cause of global cancer-related fatalities. In the year 2020, an estimated 1.93 million new cases of colorectal cancer were diagnosed, leading to 0.94 million deaths attributed to colorectal cancer worldwide. This accounts for 10% of the total global cancer incidence (comprising 19.29 million new cases) and 9.4% of all cancer-related deaths (totaling 9.96 million deaths). Notably, both the incidence and mortality rates of COAD have exhibited a consistent upward trajectory, primarily linked to the unfavorable prognosis associated with advanced COAD cases. Numerous ubiquitin-specific peptidases (USPs), or deubiquitinases, have been identified to play pivotal oncogenic roles in colon cancer. The deubiquitinase USP25, for instance, supports colonic inflammation and bacterial infection, promoting colorectal cancer through Wnt and  \n* For correspondence: Deyu Fang, [fangd@northwestern.edu](fangd@northwestern.edu).  \nSOCS3-pSTAT3 signaling (1). Several other deubiquitinases, including USP10 (2), USP22 (3, 4), USP28 (5), USP7, and CYLD (6), have been demonstrated to foster the development of colon cancer by activating oncogenic Myc. Furthermore, our research and others have revealed the critical role of USP22 in promoting colon cancer cell growth and inhibiting apoptosis through p53 suppression and the stabilization of cyclins B1 and D1 (3, 7). Similarly, USP17 exhibits high expression in colon cancer biopsies, is cell cycle-regulated, and is essential for G1-S progression (8). Moreover, deubiquitinases from the OTUD family, such as OTUD1 (9, 10), OTUD3 (11), and OTUD4 (12), have been implicated in colon inflammation and cancer. In contrast, USP9x has been found to stabilize the E3 ubiquitin ligase Fbw7, inhibiting Myc as a tumor suppressor (13).  \nATXN3, also known as Ataxin-3, ATX3, AT3, or MJD, belongs to the MJD family, which is one of the five primary cysteine deubiquitinating enzyme families. The physiological functions of ATXN3 are largely unexplored. M","cbCaidK4Z3qMtBtt","https://ap.wps.com/l/cbCaidK4Z3qMtBtt","pdf",4008692,11,"English","# Overview\n## ATXN3 and colon adenocarcinoma background\n## Molecular mechanism linking ATXN3 to Galectin-9\n## Functional experiments and reversal by Galectin-9\n## Clinical correlation in human tissues","[{\"question\":\"What is the main finding about ATXN3 in colon adenocarcinoma?\",\"answer\":\"ATXN3 acts as a tumor suppressor by promoting Galectin-9–mediated apoptosis in colon cancer.\"},{\"question\":\"How does deleting ATXN3 affect colon cancer growth?\",\"answer\":\"CRISPR-mediated ATXN3 deletion unexpectedly intensifies colon cancer growth in vitro and in xenograft models.\"},{\"question\":\"What mechanism connects ATXN3 to Galectin-9?\",\"answer\":\"ATXN3 functions as a deubiquitinase that specifically targets Galectin-9, inhibiting its ubiquitination and lowering Galectin-9 protein levels.\"}]","ATXN3 functions as a tumor suppressor through potentiating galectin-9-mediated apoptosis in human colon adenocarcinoma | PDF",1790002928,28]