Involvement of claudins 6 and 9 in epithelial-mesenchymal transition and the metastatic process.

IF 3.6 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Tissue Barriers Pub Date : 2025-07-04 DOI:10.1080/21688370.2025.2529091

Naresh E Diego, Luis F Montaño, Erika P Rendón-Huerta

{"title":"Involvement of claudins 6 and 9 in epithelial-mesenchymal transition and the metastatic process.","authors":"Naresh E Diego, Luis F Montaño, Erika P Rendón-Huerta","doi":"10.1080/21688370.2025.2529091","DOIUrl":null,"url":null,"abstract":"<p><p>Claudins are essential components of tight junctions, and their abnormal expression is linked to cancer development. Claudin-6 (CLDN6) and Claudin-9 (CLDN9) are claudins whose expression is suppressed post-development but reinduced in various malignancies. This review highlights the distinct yet complementary roles of CLDN6 and CLDN9 during epithelial-mesenchymal transition (EMT) and their contributions to cell migration and invasion in cancer. CLDN9 primarily enhances cell migration by inducing cytoskeletal rearrangement and activating pathways, including MAPK and Tyk2/STAT3. Moreover, CLDN9 overexpression is associated with pseudopodia formation, glycolytic remodeling, and immune evasion. Conversely, CLDN6 is more strongly linked to cell invasiveness and matrix degradation, primarily through the induction of MMPs via the EGFR/mTOR and PI3K/AKT pathways. CLDN6 also plays a role in stemness and therapy resistance in specific cancers. While CLDN6 and CLDN9 can function independently, their co-expression is connected with aggressive tumor behavior and poor prognosis, suggesting a synergistic process that promotes migration and invasion.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2529091"},"PeriodicalIF":3.6000,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Tissue Barriers","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1080/21688370.2025.2529091","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}

引用次数: 0

Abstract

Claudins are essential components of tight junctions, and their abnormal expression is linked to cancer development. Claudin-6 (CLDN6) and Claudin-9 (CLDN9) are claudins whose expression is suppressed post-development but reinduced in various malignancies. This review highlights the distinct yet complementary roles of CLDN6 and CLDN9 during epithelial-mesenchymal transition (EMT) and their contributions to cell migration and invasion in cancer. CLDN9 primarily enhances cell migration by inducing cytoskeletal rearrangement and activating pathways, including MAPK and Tyk2/STAT3. Moreover, CLDN9 overexpression is associated with pseudopodia formation, glycolytic remodeling, and immune evasion. Conversely, CLDN6 is more strongly linked to cell invasiveness and matrix degradation, primarily through the induction of MMPs via the EGFR/mTOR and PI3K/AKT pathways. CLDN6 also plays a role in stemness and therapy resistance in specific cancers. While CLDN6 and CLDN9 can function independently, their co-expression is connected with aggressive tumor behavior and poor prognosis, suggesting a synergistic process that promotes migration and invasion.

查看原文本刊更多论文

claudin 6和9参与上皮-间质转化和转移过程。

claudin是紧密连接的重要组成部分，其异常表达与癌症的发展有关。Claudin-6 （CLDN6）和Claudin-9 （CLDN9）是在各种恶性肿瘤中表达被抑制但又被诱导的claudin。这篇综述强调了CLDN6和CLDN9在上皮-间质转化（EMT）过程中不同但互补的作用，以及它们对癌症细胞迁移和侵袭的贡献。CLDN9主要通过诱导细胞骨架重排和激活包括MAPK和Tyk2/STAT3在内的通路来促进细胞迁移。此外，CLDN9过表达与假足形成、糖酵解重塑和免疫逃避有关。相反，CLDN6与细胞侵袭性和基质降解密切相关，主要通过EGFR/mTOR和PI3K/AKT途径诱导MMPs。CLDN6也在特定癌症的干细胞和治疗抵抗中发挥作用。虽然CLDN6和CLDN9可以独立发挥作用，但它们的共表达与肿瘤的侵袭性行为和不良预后有关，提示其具有促进迁移和侵袭的协同过程。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Tissue Barriers MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

6.60

自引率

6.50%

发文量

期刊介绍： Tissue Barriers is the first international interdisciplinary journal that focuses on the architecture, biological roles and regulation of tissue barriers and intercellular junctions. We publish high quality peer-reviewed articles that cover a wide range of topics including structure and functions of the diverse and complex tissue barriers that occur across tissue and cell types, including the molecular composition and dynamics of polarized cell junctions and cell-cell interactions during normal homeostasis, injury and disease state. Tissue barrier formation in regenerative medicine and restoration of tissue and organ function is also of interest. Tissue Barriers publishes several categories of articles including: Original Research Papers, Short Communications, Technical Papers, Reviews, Perspectives and Commentaries, Hypothesis and Meeting Reports. Reviews and Perspectives/Commentaries will typically be invited. We also anticipate to publish special issues that are devoted to rapidly developing or controversial areas of research. Suggestions for topics are welcome. Tissue Barriers objectives: Promote interdisciplinary awareness and collaboration between researchers working with epithelial, epidermal and endothelial barriers and to build a broad and cohesive worldwide community of scientists interesting in this exciting field. Comprehend the enormous complexity of tissue barriers and map cross-talks and interactions between their different cellular and non-cellular components. Highlight the roles of tissue barrier dysfunctions in human diseases. Promote understanding and strategies for restoration of tissue barrier formation and function in regenerative medicine. Accelerate a search for pharmacological enhancers of tissue barriers as potential therapeutic agents. Understand and optimize drug delivery across epithelial and endothelial barriers.