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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...

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Autores principales: Fujiwara-Tani, Rina, Mori, Shiori, Ogata, Ruiko, Sasaki, Rika, Ikemoto, Ayaka, Kishi, Shingo, Kondoh, Masuo, Kuniyasu, Hiroki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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.
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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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