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This review links context-dependent roles in malignancies with physiological functions, pathological outcomes of dysregulated expression, and regulatory involvement in the tumor immune microenvironment, supporting T-BOX-targeted therapy development.",{"@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/research-report/","Research & Report",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/context-dependent-t-box-transcription-factor-family-from-biology-to-targeted-therapy/333509/",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/context-dependent-t-box-transcription-factor-family-from-biology-to-targeted-therapy/333509.png","ImageObject",300,407,{"name":42,"@type":43},"Violet","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-31","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",7,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What are T-BOX transcription factors and what broad biological roles do they play?","Question",{"text":63,"@type":64},"T-BOX factors are an evolutionarily conserved family with a characteristic T-BOX DNA-binding domain. 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Cell Communication and Signaling (2024) 22:350  \n[https://doi.org/10.1186/s12964-024-01719-2](https://doi.org/10.1186/s12964-024-01719-2)  \nCell Communication and Signaling  \nREVIEW Open Access  \nContext-dependent T-BOX transcription factor  family: from biology to targeted therapy  \nSiwen Li 1, Xiangyuan Luo 1, Mengyu Sun 1, Yijun Wang 1, Zerui Zhang 1, Junqing Jiang 1, Dian Hu 1, Jiaqian Zhang 1, Zhangfan Wu 1, Yufei Wang 1, Wenjie Huang 1,2* and Limin Xia 1,3*  \nAbstract  \nT-BOX factors belong to an evolutionarily conserved family of transcription factors. T-BOX factors not only play key roles in growth and development but are also involved in immunity, cancer initiation, and progression. Moreover, the same T-BOX molecule exhibits different or even opposite effects in various developmental processes and tumor microenvironments. Understanding the multiple roles of context-dependent T-BOX factors in malignancies is vital for uncovering the potential ofT-BOX-targeted cancer therapy. We summarize the physiological roles of T-BOX factors in different developmental processes and their pathological roles observed when their expression is dysregulated. We also discuss their regulatory roles in tumor immune microenvironment (TIME) and the newly arising questions that remain unresolved. This review will help in systematically and comprehensively understanding the vital role of the T-BOX transcription factor family in tumor physiology, pathology, and immunity. The intention is to provide valuable information to support the development ofT-BOX-targeted therapy.  \n*Correspondence:  \nWenjie Huang [huangwenjie@tjh.tjmu.edu.cn](huangwenjie@tjh.tjmu.edu.cn)[ ](huangwenjie@tjh.tjmu.edu.cn)Limin Xia[xialimin@tjh.tjmu.edu.cn](xialimin@tjh.tjmu.edu.cn)  \n1Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province 430030, China  \n2Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Clinical Medicine Research Center for Hepatic Surgery of Hubei Province, Key Laboratory of Organ Transplantation, Huazhong University of Science and Technology, Ministry of Education and Ministry of Public Health, Wuhan,  \nHubei 430030, China  \n3State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an 710032, China  \nIntroduction  \nT-BOX transcription factors are evolutionarily highly conserved and are characterized by a conserved DNAbinding domain termed T-BOX, identifying and specifically binding to its target DNA domain. TBXT, also known as Brachyury (meaning short tail), was first described in 1927 by the scientist Dobrovolskaia-Zavadskaia in a mutant mouse strain. The TBXT mutation in mouse results in a shorter tail or complete absence of the tails [1]. Since then, many T-BOX transcription factors have been uncovered, and their essential functions in physiological and pathological conditions have gradually been revealed. Physiologically, T-BOX factors are involved in many developmental processes, including embryonic, organogenic, and limb development [2]. However, if dysregulation of T-BOX factors occurs, normal body function may be disrupted, and the individual becomes vulnerable to several diseases, including cancer. For example, TBX1 and TBX5 haploid insufficiency respectively causes DiGeorge syndrome charactered as  \n© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, 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 ","cbCaipfzLvHAab54","https://ap.wps.com/l/cbCaipfzLvHAab54","pdf",9755888,23,"English","# Introduction\n## Context-dependent roles in development and cancer\n# Abstract","[{\"question\":\"What are T-BOX transcription factors and what broad biological roles do they play?\",\"answer\":\"T-BOX factors are an evolutionarily conserved family with a characteristic T-BOX DNA-binding domain. They regulate growth and development and also participate in immunity, cancer initiation, and progression.\"},{\"question\":\"How can the same T-BOX molecule have different effects?\",\"answer\":\"The review states that the same T-BOX molecule can show different or even opposite effects depending on the developmental process and the tumor microenvironment.\"},{\"question\":\"What does the review focus on regarding T-BOX in cancer therapy?\",\"answer\":\"It summarizes physiological roles and pathological consequences of dysregulated T-BOX expression, discusses regulatory roles in the tumor immune microenvironment, and addresses unresolved questions relevant to developing T-BOX-targeted cancer therapy.\"}]","Context-dependent T-BOX transcription factor family - from biology to targeted therapy | PDF",1790002815,58]