The strong propensity of Cadherin‐23 for aggregation inhibits cell migration

Cadherin‐23 (Cdh23), a long‐chain non‐classical cadherin, exhibits strong homophilic and heterophilic binding. The physiological relevance of strong heterophilic binding with protocadherin‐15 at neuroepithelial tip links is well‐studied. However, the role of Cdh23 homodimers in physiology is less un...

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Main Authors: Malay K. Sannigrahi, Cheerneni S. Srinivas, Nilesh Deokate, Sabyasachi Rakshit
Format: Article
Language:English
Published: Wiley 2019-05-01
Series:Molecular Oncology
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Online Access:https://doi.org/10.1002/1878-0261.12469
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author Malay K. Sannigrahi
Cheerneni S. Srinivas
Nilesh Deokate
Sabyasachi Rakshit
author_facet Malay K. Sannigrahi
Cheerneni S. Srinivas
Nilesh Deokate
Sabyasachi Rakshit
author_sort Malay K. Sannigrahi
collection DOAJ
description Cadherin‐23 (Cdh23), a long‐chain non‐classical cadherin, exhibits strong homophilic and heterophilic binding. The physiological relevance of strong heterophilic binding with protocadherin‐15 at neuroepithelial tip links is well‐studied. However, the role of Cdh23 homodimers in physiology is less understood, despite its widespread expression at the cell boundaries of various human and mouse tissues, including kidney, muscle, testes, and heart. Here, we performed immunofluorescence studies that revealed that Cdh23 is present as distinct puncta at the cell–cell boundaries of cancer cells. Analysis of patient data and quantitative estimation of Cdh23 in human tissues (normal and tumor) also indicated that Cdh23 is down‐regulated via promoter methylation in lung adenocarcinoma (AD) and esophageal squamous cell carcinoma (SCC) cells; we also observed a clear inverse correlation between Cdh23 expression and cancer metastasis. Using HEK293T cells and four types of cancer cells differentially expressing Cdh23, we observed that cell migration was faster in cells with reduced levels of Cdh23 expression. The cell migration rate in cancer cells is further accelerated by the presence of excretory isoforms of Cdh23, which loosen its cell‐adhesion ability by competitive binding. Overall, our data indicate the role of Cdh23 as a suppressor of cell migration.
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spelling doaj-art-2e87e59cc4a94ffcad1d66f304d276082025-08-20T02:07:05ZengWileyMolecular Oncology1574-78911878-02612019-05-011351092110910.1002/1878-0261.12469The strong propensity of Cadherin‐23 for aggregation inhibits cell migrationMalay K. Sannigrahi0Cheerneni S. Srinivas1Nilesh Deokate2Sabyasachi Rakshit3Department of Chemical Sciences Indian Institute of Science Education and Research Mohali Chandigarh IndiaDepartment of Chemical Sciences Indian Institute of Science Education and Research Mohali Chandigarh IndiaDepartment of Biological Sciences Indian Institute of Science Education and Research Mohali Chandigarh IndiaDepartment of Chemical Sciences Indian Institute of Science Education and Research Mohali Chandigarh IndiaCadherin‐23 (Cdh23), a long‐chain non‐classical cadherin, exhibits strong homophilic and heterophilic binding. The physiological relevance of strong heterophilic binding with protocadherin‐15 at neuroepithelial tip links is well‐studied. However, the role of Cdh23 homodimers in physiology is less understood, despite its widespread expression at the cell boundaries of various human and mouse tissues, including kidney, muscle, testes, and heart. Here, we performed immunofluorescence studies that revealed that Cdh23 is present as distinct puncta at the cell–cell boundaries of cancer cells. Analysis of patient data and quantitative estimation of Cdh23 in human tissues (normal and tumor) also indicated that Cdh23 is down‐regulated via promoter methylation in lung adenocarcinoma (AD) and esophageal squamous cell carcinoma (SCC) cells; we also observed a clear inverse correlation between Cdh23 expression and cancer metastasis. Using HEK293T cells and four types of cancer cells differentially expressing Cdh23, we observed that cell migration was faster in cells with reduced levels of Cdh23 expression. The cell migration rate in cancer cells is further accelerated by the presence of excretory isoforms of Cdh23, which loosen its cell‐adhesion ability by competitive binding. Overall, our data indicate the role of Cdh23 as a suppressor of cell migration.https://doi.org/10.1002/1878-0261.12469cadherin‐23cell migrationcell–cell adhesionlung cancernon‐classical cadherinspromoter methylation
spellingShingle Malay K. Sannigrahi
Cheerneni S. Srinivas
Nilesh Deokate
Sabyasachi Rakshit
The strong propensity of Cadherin‐23 for aggregation inhibits cell migration
Molecular Oncology
cadherin‐23
cell migration
cell–cell adhesion
lung cancer
non‐classical cadherins
promoter methylation
title The strong propensity of Cadherin‐23 for aggregation inhibits cell migration
title_full The strong propensity of Cadherin‐23 for aggregation inhibits cell migration
title_fullStr The strong propensity of Cadherin‐23 for aggregation inhibits cell migration
title_full_unstemmed The strong propensity of Cadherin‐23 for aggregation inhibits cell migration
title_short The strong propensity of Cadherin‐23 for aggregation inhibits cell migration
title_sort strong propensity of cadherin 23 for aggregation inhibits cell migration
topic cadherin‐23
cell migration
cell–cell adhesion
lung cancer
non‐classical cadherins
promoter methylation
url https://doi.org/10.1002/1878-0261.12469
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