[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-353988-105":59,"doc-detail-353988-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","cbx8-suppresses-autophagy-dependent-senescence-in-colorectal-cancer-by-modulating-the-mtor-signaling-pathway","CBX8 suppresses autophagy-dependent senescence in colorectal cancer by modulating the mTOR signaling pathway","","Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide, and cellular senescence—an irreversible growth arrest state—is explored as a therapeutic avenue. This study systematically investigates the oncogenic function of Chromobox homolog 8 (CBX8) in CRC and how CBX8 regulates senescence and transcriptional programs. CBX8 loss suppresses CRC tumorigenesis and promotes senescence in vivo and in vitro. Mechanistically, CBX8 inhibits autophagy-dependent senescence by repressing DDIT4 through TRIM28 recruitment to maintain H3K27me3 marks. The work supports combining CBX8 inhibitors with senescence-targeting agents to enhance antitumor efficacy in CRC xenografts.",{"@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/cbx8-suppresses-autophagy-dependent-senescence-in-colorectal-cancer-by-modulating-the-mtor-signaling-pathway/353988/",{"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/cbx8-suppresses-autophagy-dependent-senescence-in-colorectal-cancer-by-modulating-the-mtor-signaling-pathway/353988.png","ImageObject",300,407,{"name":92,"@type":93},"Maya Linwood","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-24","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":14},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the main finding about CBX8 in colorectal cancer?","Question",{"text":112,"@type":113},"CBX8 deficiency suppresses colorectal tumorigenesis and promotes tumor cell senescence in both in vivo and in vitro models.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does CBX8 modulate autophagy-dependent senescence mechanistically?",{"text":117,"@type":113},"CBX8 inhibits autophagy-dependent senescence by modulating the mTOR signaling pathway via transcriptional repression of DDIT4.",{"name":119,"@type":110,"acceptedAnswer":120},"What therapeutic implication does the study suggest for CRC treatment?",{"text":121,"@type":113},"CBX8 inhibitors, especially in combination with senescence-targeting agents, enhance antitumor effects in CRC xenograft models.","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},353988,1790211607,{"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":14,"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},962084928432,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Ivyspring  \nInternational Publisher  \nInternationalJournal of Biological Sciences  \n2026; 22(6): 3127-3143. doi: 10.7150/ijbs.126032  \nResearch Paper  \nCBX8 suppresses autophagy-dependent senescence in colorectal cancer by modulating the mTOR signaling pathway  \nTiankang Li1,3, Enjian Zhang1,2, Xin Liu4, Hui Zhou1,2, Pengbo Zhang1,2, Chong Zhang1,2, Xiuzhong Zhang1,2, Nai Wu1,2, Shuai Gong1,2, Zeqiang Ren1,2, Jie Ding5􀀍, Yi Zhang1,2,6􀀍  \n1. Department of Gastrointestinal Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China.  \n2. Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, 221000, China.  \n3. Department of Breast Surgery, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, China.  \n4. Department of Endocrinology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China.  \n5. Department of Gastrointestinal Surgery, Guizhou Provincial People's Hospital; NHC Key Laboratory of Pulmonary Immunological Diseases, Guizhou Provincial People's Hospital, Guiyang, 550002, China.  \n6. Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.  \n􀀍 Corresponding authors: Yi Zhang, E-mail: [dr_zhy@xzhmu.edu.cn](dr_zhy@xzhmu.edu.cn); Jie Ding, E-mail: [dingjiexy@126.com](dingjiexy@126.com).  \n© The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License ([https://creativecommons.org/licenses/by/4.0/](https://creativecommons.org/licenses/by/4.0/)). See [https://ivyspring.com/terms](https://ivyspring.com/terms) for full terms and conditions.  \nReceived: 2025.09.29; Accepted: 2026.02.04; Published: 2026.02.26  \nAbstract  \nColorectal cancer (CRC) is among the most common cancers worldwide. Cellular senescence, characterized by an irreversible state of growth arrest, has been recognized as a promising therapeutic strategy for combating cancer. Here, the oncogenic role of Chromobox homolog 8 (CBX8) in CRC and its regulatory mechanisms in cell senescence and transcriptional regulation were systematically investigated. We demonstrated that CBX8 deficiency suppresses colorectal tumorigenesis and promotes tumor cell senescence in both in vivo and in vitro models. Mechanistically, CBX8 inhibits autophagy-dependent senescence in CRC by modulating the mTOR signaling pathway through transcriptional repression of DDIT4, a known negative regulator of mTOR. CBX8 achieves this by recruiting TRIM28 to bind the promoter region of DDIT4, thereby maintaining the H3K27me3 modification status and repressing expression of DDIT4 . Furthermore, our findings highlight the therapeutic potential of CBX8 inhibitors in combination with senescence-targeting agents, which significantly enhances antitumor effects in CRC xenograft models. These results provide novel insights into the molecular mechanisms underlying CRC progression and underscore the potential of CBX8 as a therapeutic target for developing targeted therapies and senolytic-based anticancer strategies. This study advances our understanding of CRC pathogenesis and offers promising directions for precision medicine in CRC treatment.  \nKeywords: colorectal cancer; CBX8; autophagy; senescence; senolytic  \nIntroduction  \nColorectal cancer (CRC) ranks as the fourth leading cause of cancer-related mortality worldwide, accounting for approximately 9.2% of all cancer deaths [1] . The incidence rates of CRC are rapidly increasing due to gradual lifestyle changes.  \nCellular senescence is characterized by a stable cell-cycle arrest accompanied by distinct morphological and phenotypic alterations, including  \nincreased cell size, accumulation of cytoplasmic vacuoles, and the secretion of a variety of factors collectively termed senescence-associated secretory phenotypes (SASPs) [2] . CRC is recognized as a quintessential age-related disease [3]; the association between CRC and cellular s","cbCaieNpKLgHFPT1","https://ap.wps.com/l/cbCaieNpKLgHFPT1","pdf",10769441,17,"English","# Abstract\n# Keywords\n# Introduction\n## Cellular senescence and CRC progression\n## Autophagy and senescence relationship\n## CBX8 as a transcriptional regulator in cancer\n## Rationale for investigating CBX8 in tumor senescence","[{\"question\":\"What is the main finding about CBX8 in colorectal cancer?\",\"answer\":\"CBX8 deficiency suppresses colorectal tumorigenesis and promotes tumor cell senescence in both in vivo and in vitro models.\"},{\"question\":\"How does CBX8 modulate autophagy-dependent senescence mechanistically?\",\"answer\":\"CBX8 inhibits autophagy-dependent senescence by modulating the mTOR signaling pathway via transcriptional repression of DDIT4.\"},{\"question\":\"What therapeutic implication does the study suggest for CRC treatment?\",\"answer\":\"CBX8 inhibitors, especially in combination with senescence-targeting agents, enhance antitumor effects in CRC xenograft models.\"}]","CBX8 suppresses autophagy-dependent senescence in colorectal cancer by modulating the mTOR signaling pathway | PDF",1790108362,43]