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It influences embryogenesis, tissue development, and multiple disease processes, acting through pathways including Hippo and Wnt. This review summarizes FAT4 roles in tissue morphogenesis, autoimmune disorders, and cancers, highlighting that inactivation via mutation, methylation, or deletion links to developmental anomalies, immune dysregulation, and tumor progression. The work aims to clarify mechanisms and assess clinical diagnostic and therapeutic potential, proposing prognostic marker and target value.",{"@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/research-on-the-role-and-mechanism-of-fat4-in-the-development-and-progression-of-tumor-and-non-tumor-diseases/349318/",{"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/research-on-the-role-and-mechanism-of-fat4-in-the-development-and-progression-of-tumor-and-non-tumor-diseases/349318.png","ImageObject",300,407,{"name":92,"@type":93},"Mimi","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 is FAT4 and what key functions does it have?","Question",{"text":112,"@type":113},"FAT4 is an atypical cadherin family member that acts as a calcium-dependent adhesion receptor. It regulates planar cell polarity and contributes to embryonic development and tissue homeostasis while modulating proliferation, polarity, immune microenvironment, and morphogenesis.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How is FAT4 connected to cancer development and progression?",{"text":117,"@type":113},"FAT4 inactivation (mutation, methylation, or deletion) is associated with developmental anomalies, immune responses, and cancer progression. It promotes tumor progression by impairing cell adhesion, facilitating EMT, and activating oncogenic signaling pathways such as Hippo/YAP and Wnt/β-catenin.",{"name":119,"@type":110,"acceptedAnswer":120},"Which signaling pathways are highlighted in the FAT4 mechanism?",{"text":121,"@type":113},"The document emphasizes mechanistic links between FAT4 and multiple signaling pathways, particularly Hippo (including YAP/TAZ activity) and Wnt/β-catenin. It also references effects on planar cell polarity (PCP) and related network integration needs.","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},349318,1790156734,{"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},2336477974920,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Zhong et al. Discover Oncology (2026) 17:913 [https://doi.org/10.1007/s12672-026-05103-z](https://doi.org/10.1007/s12672-026-05103-z)  \nDiscover Oncology  \nREVIEW Open Access  \nResearch on the role and mechanism of FAT4   in the development and progression of tumor and non-tumor diseases  \nLingli Zhong1*†, Renshan Wang2†, Yidie Li1†, Zhenyu Li1, Le Zhang1, Nuo Chen1 and Jing Wang2*  \n†Lingli Zhong, Renshan Wang andYidie Li have contributed equally to this work and first authorship.  \n*Correspondence:  \nLingli Zhong [18782917262@163.com](18782917262@163.com)  \nJing Wang  \n[antcity@126.com](antcity@126.com)  \n1Department of Anorectal Surgery, West China Hospital Sichuan University Jintang Hospital, Jintang First People’s Hospital, Chengdu, China  \n2Department of Anorectal Surgery, The Affiliated People’s Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, China  \nAbstract  \nFAT4 (FAT Atypical Cadherin 4), a member of the atypical cadherin family, represents the human ortholog of Drosophila Fat (Ft) and functions as a positive regulator of planar cell polarity in the Drosophila wing. It serves various functions during embryogenesis and adult tissue development, demonstrating calcium-dependent adhesive properties. FAT4 has been extensively studied regarding its physiological functions and tumor mechanisms, with numerous studies emphasizing its essential role in various biological processes. A systematic mechanistic analysis and review of its key functions across these various biological processes is lacking. FAT4, asa transmembrane adhesion receptor and tumor suppressor, is expressed in cells across multiple systems, diseases, and diverse cancer tissues. It performs essential functions in diverse biological processes by modulating cell proliferation, polarity, and the immune microenvironment through multiple signaling pathways. This review delineates the functions of FAT4 in tissue morphogenesis, autoimmune diseases, and malignancies. The inactivation of this gene (through mutation, methylation, and deletion) is closely associated with multisystem developmental anomalies, immune responses, and cancer progression, thereby establishing it as a potential prognostic marker and therapeutic target. This study aimed to enhance the understanding of FAT4 and evaluate its potential applications in clinical diagnosis and treatment.  \nKeywords FAT4, DCSH1, Hippo, Wnt, PCP, Tumor suppressor  \n1 Introduction  \nFAT4 (FAT Atypical Cadherin 4), an atypical cadherin family member, is the human ortholog of the Drosophila Fat gene [1].It was first discovered for its function in regulating planar cell polarity (PCP) during Drosophila wing morphogenesis [2, 3].The protein exhibits calcium-dependent adhesive properties and is essential for embryonic development, tissue homeostasis maintenance, and multisystem diseases. FAT4 modulates cell proliferation, polarity establishment, immune microenvironment, and tissue morphogenesis by activating the Hippo signaling pathway, inhibiting yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) nuclear translocation,  \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 exce","cbCailzbA1cs0KBT","https://ap.wps.com/l/cbCailzbA1cs0KBT","pdf",2109173,34,"English","# Abstract\n# Keywords\n# 1 Introduction\n## FAT4 functions and discovery\n## Disease associations and tumor suppression","[{\"question\":\"What is FAT4 and what key functions does it have?\",\"answer\":\"FAT4 is an atypical cadherin family member that acts as a calcium-dependent adhesion receptor. It regulates planar cell polarity and contributes to embryonic development and tissue homeostasis while modulating proliferation, polarity, immune microenvironment, and morphogenesis.\"},{\"question\":\"How is FAT4 connected to cancer development and progression?\",\"answer\":\"FAT4 inactivation (mutation, methylation, or deletion) is associated with developmental anomalies, immune responses, and cancer progression. It promotes tumor progression by impairing cell adhesion, facilitating EMT, and activating oncogenic signaling pathways such as Hippo/YAP and Wnt/β-catenin.\"},{\"question\":\"Which signaling pathways are highlighted in the FAT4 mechanism?\",\"answer\":\"The document emphasizes mechanistic links between FAT4 and multiple signaling pathways, particularly Hippo (including YAP/TAZ activity) and Wnt/β-catenin. It also references effects on planar cell polarity (PCP) and related network integration needs.\"}]","Research on the role and mechanism of FAT4 in the development and progression of tumor and non-tumor diseases | PDF",1790082738,86]