[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-382200-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-382200-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","claudin-4-a-new-molecular-target-for-epithelial-cancer-therapy-review","Claudin-4: A New Molecular Target for Epithelial Cancer Therapy - Review","","Claudin-4 (CLDN4) is a crucial tight-junction component in epithelial cells. CLDN4 is frequently overexpressed in epithelial malignancies and associates with cancer progression, driven by epigenetic alterations, inflammation-related infection/cytokines, and growth factor signaling. CLDN4 sustains the tumor microenvironment via tight junction formation and can impede anticancer drug entry. Reduced CLDN4 may mark epithelial-mesenchymal transition (EMT), while non–tight-junction CLDN4 promotes integrin beta 1- and YAP-mediated proliferation, EMT, and stemness. These functions support molecular therapeutic strategies targeting CLDN4.",{"@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/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/claudin-4-a-new-molecular-target-for-epithelial-cancer-therapy-review/382200/",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/claudin-4-a-new-molecular-target-for-epithelial-cancer-therapy-review/382200.png","ImageObject",300,407,{"name":42,"@type":43},"Finn","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-25","2026-09-24",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",6,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What roles does CLDN4 play in epithelial cancers?","Question",{"text":63,"@type":64},"CLDN4 helps maintain the tumor microenvironment by forming tight junctions and can act as a barrier to anticancer drug entry. Non–tight-junction CLDN4 also activates pathways that promote proliferation, EMT, and stemness.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How is CLDN4 expression regulated?",{"text":68,"@type":64},"CLDN4 expression is regulated by epigenetic mechanisms and inflammation-related processes, including factors such as DNA methylation changes in the CLDN4 promoter region.",{"name":70,"@type":61,"acceptedAnswer":71},"What therapeutic strategies target CLDN4?",{"text":72,"@type":64},"The review describes targeting CLDN4 using anti-CLDN4 extracellular domain antibodies, gene knockdown approaches, and CPE/C-CPE-based strategies, with reported experimental efficacy.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},382200,1790797844,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,105,109,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":102,"show_sort_weight":103,"slug":104},"Technology",50,"technology",{"id":106,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":107,"slug":108},7,40,"healthcare",{"id":110,"doc_module":4,"doc_module_name":25,"category_name":111,"show_sort_weight":112,"slug":113},8,"Research & Report",30,"research-report",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},9,"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":106,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":145},34359740700684,"https://ap-avatar.wpscdn.com/avatar/1f400023980c374ae676?_k=1777273430885731487","Review  \nClaudin-4: A New Molecular Target for Epithelial Cancer Therapy  \nRina Fujiwara-Tani 1,*, Shiori Mori 1, Ruiko Ogata 1, Rika Sasaki 1, Ayaka Ikemoto 1, Shingo Kishi 1, Masuo Kondoh 2 and Hiroki Kuniyasu 1, *  \nCitation: Fujiwara-Tani, R.; Mori, S.; Ogata, R.; Sasaki, R.; Ikemoto, A.; Kishi, S.; Kondoh, M.; Kuniyasu, H. Claudin-4: A New Molecular Target for Epithelial Cancer Therapy. Int. J. Mol. Sci. 2023, 24, 5494. [https://](https://)[ ](https://)[doi.org/10.3390/ijms24065494](doi.org/10.3390/ijms24065494)  \nAcademic Editor: Anastasios Lymperopoulos  \nReceived: 23 February 2023  \nRevised: 10 March 2023  \nAccepted: 10 March 2023  \nPublished: 13 March 2023  \nCopyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Department of Molecular Pathology, Nara Medical University, Kashihara 634-8521, Japan; [m.0310.s.h5@gmail.com](m.0310.s.h5@gmail.com) (S.M.); [pkuma.og824@gmail.com](pkuma.og824@gmail.com) (R.O.); [rika0st1113v726296v@icloud.com](rika0st1113v726296v@icloud.com) (R.S.); [dc117023@naramed-u.ac.jp](dc117023@naramed-u.ac.jp) (A.I.); [nmu6429@yahoo.co.jp](nmu6429@yahoo.co.jp) (S.K.)  \n2 Drug Innovation Center, Graduate School of Pharmaceutical Sciences, Osaka University, 6-1 Yamadaoka, Suita 565-0871, Japan; [claudindds@gmail.com](claudindds@gmail.com)  \n* Correspondence: [rina_fuji@naramed-u.ac.jp](rina_fuji@naramed-u.ac.jp) (R.F.-T.); [cooninh@zb4.so-net.ne.jp](cooninh@zb4.so-net.ne.jp) (H.K.); Tel.: +81-744-22-3051 (R.F.-T. & H.K.); Fax: +81-744-25-7308 (R.F.-T. & H.K.)  \nAbstract: Claudin-4 (CLDN4) is a key component of tight junctions (TJs) in epithelial cells. CLDN4 is overexpressed in many epithelial malignancies and correlates with cancer progression. Changes in CLDN4 expression have been associated with epigenetic factors (such as hypomethylation of promoter DNA), inflammation associated with infection and cytokines, and growth factor signaling. CLDN4 helps to maintain the tumor microenvironment by forming TJs and acts as a barrier to the entry of anticancer drugs into tumors. Decreased expression of CLDN4 is a potential marker of epithelial-mesenchymal transition (EMT), and decreased epithelial differentiation due to reduced CLDN4 activity is involved in EMT induction. Non-TJ CLDN4 also activates integrin beta 1 and YAP to promote proliferation, EMT, and stemness. These roles in cancer have led to investigations of molecular therapies targeting CLDN4 using anti-CLDN4 extracellular domain antibodies, gene knockdown, clostridium perfringens enterotoxin (CPE), and C-terminus domain of CPE (C-CPE), which have demonstrated the experimental efficacy of this approach. CLDN4 is strongly involved in promoting malignant phenotypes in many epithelial cancers and is regarded as a promising molecular therapeutic target.  \nKeywords: claudin-4; cancer; molecular target; tight junction; non-tight junction claudin  \n1. Introduction  \nTight junctions (TJs) are multiprotein complexes present at the tip of the lateral membrane of polarized epithelial and endothelial cells [1] . The main function of these structures is to mediate adhesion and polarity between cells. Therefore, it is believed that the impairment of TJs and the concomitant loss of cell-to-cell adhesion are necessary for the early stages of cancer invasion and metastasis. However, it is becoming increasingly clear that TJ proteins such as claudins play important roles not only in adhesion but also in the activation of intracellular signaling, which contributes to tumor progression and metastasis. Claudin (CLDN) is a cell-to-cell adhesion component of the tight junctions and forms a protein family with 27 highly homologous members [2,3] . CLDN4 is the major CLDN i","cbCaibYdryZ0mzeT","https://ap.wps.com/l/cbCaibYdryZ0mzeT","pdf",1910334,15,"English","# Introduction\n# Claudin-4 Expression and Regulation in Cancer\n## Epigenetics","[{\"question\":\"What roles does CLDN4 play in epithelial cancers?\",\"answer\":\"CLDN4 helps maintain the tumor microenvironment by forming tight junctions and can act as a barrier to anticancer drug entry. Non–tight-junction CLDN4 also activates pathways that promote proliferation, EMT, and stemness.\"},{\"question\":\"How is CLDN4 expression regulated?\",\"answer\":\"CLDN4 expression is regulated by epigenetic mechanisms and inflammation-related processes, including factors such as DNA methylation changes in the CLDN4 promoter region.\"},{\"question\":\"What therapeutic strategies target CLDN4?\",\"answer\":\"The review describes targeting CLDN4 using anti-CLDN4 extracellular domain antibodies, gene knockdown approaches, and CPE/C-CPE-based strategies, with reported experimental efficacy.\"}]","Claudin-4: A New Molecular Target for Epithelial Cancer Therapy - Review | PDF",1790249489,38]