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Claudin-4: A New Molecular Target for Epithelial Cancer Therapy
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), inflam...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10051602/ https://www.ncbi.nlm.nih.gov/pubmed/36982569 http://dx.doi.org/10.3390/ijms24065494 |
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author | Fujiwara-Tani, Rina Mori, Shiori Ogata, Ruiko Sasaki, Rika Ikemoto, Ayaka Kishi, Shingo Kondoh, Masuo Kuniyasu, Hiroki |
author_facet | Fujiwara-Tani, Rina Mori, Shiori Ogata, Ruiko Sasaki, Rika Ikemoto, Ayaka Kishi, Shingo Kondoh, Masuo Kuniyasu, Hiroki |
author_sort | Fujiwara-Tani, Rina |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10051602 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-100516022023-03-30 Claudin-4: A New Molecular Target for Epithelial Cancer Therapy Fujiwara-Tani, Rina Mori, Shiori Ogata, Ruiko Sasaki, Rika Ikemoto, Ayaka Kishi, Shingo Kondoh, Masuo Kuniyasu, Hiroki Int J Mol Sci Review 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. MDPI 2023-03-13 /pmc/articles/PMC10051602/ /pubmed/36982569 http://dx.doi.org/10.3390/ijms24065494 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Fujiwara-Tani, Rina Mori, Shiori Ogata, Ruiko Sasaki, Rika Ikemoto, Ayaka Kishi, Shingo Kondoh, Masuo Kuniyasu, Hiroki Claudin-4: A New Molecular Target for Epithelial Cancer Therapy |
title | Claudin-4: A New Molecular Target for Epithelial Cancer Therapy |
title_full | Claudin-4: A New Molecular Target for Epithelial Cancer Therapy |
title_fullStr | Claudin-4: A New Molecular Target for Epithelial Cancer Therapy |
title_full_unstemmed | Claudin-4: A New Molecular Target for Epithelial Cancer Therapy |
title_short | Claudin-4: A New Molecular Target for Epithelial Cancer Therapy |
title_sort | claudin-4: a new molecular target for epithelial cancer therapy |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10051602/ https://www.ncbi.nlm.nih.gov/pubmed/36982569 http://dx.doi.org/10.3390/ijms24065494 |
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