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Alteration of Cadherin 3 Expression and DNA Methylation in Association with Aggressive Renal Cell Carcinoma

Cadherins (calcium-dependent adhesion proteins) are important in cellular adhesion and may play a role in the development and progression of renal cell carcinoma (RCC). This study investigated changes in cadherin 3 (CDH3; P-cadherin) mRNA expression, DNA methylation, and protein expression in RCC an...

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Autores principales: Faraj Tabrizi, Pouriya, Peters, Inga, Schimansky, Inga, Dubrowinskaja, Natalia, Reese, Christel, Tezval, Hossein, Kuczyk, Markus Antonius, Serth, Jürgen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10670999/
https://www.ncbi.nlm.nih.gov/pubmed/38003666
http://dx.doi.org/10.3390/ijms242216476
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author Faraj Tabrizi, Pouriya
Peters, Inga
Schimansky, Inga
Dubrowinskaja, Natalia
Reese, Christel
Tezval, Hossein
Kuczyk, Markus Antonius
Serth, Jürgen
author_facet Faraj Tabrizi, Pouriya
Peters, Inga
Schimansky, Inga
Dubrowinskaja, Natalia
Reese, Christel
Tezval, Hossein
Kuczyk, Markus Antonius
Serth, Jürgen
author_sort Faraj Tabrizi, Pouriya
collection PubMed
description Cadherins (calcium-dependent adhesion proteins) are important in cellular adhesion and may play a role in the development and progression of renal cell carcinoma (RCC). This study investigated changes in cadherin 3 (CDH3; P-cadherin) mRNA expression, DNA methylation, and protein expression in RCC and compared the results with the histopathological and clinical characteristics of patients. The possible contribution of CDH3 to tumor cell invasiveness was tested in a functional assay using siRNA-based suppression of CDH3 expression and subsequent real-time impedance analysis using a Matrigel invasion model. Our analyses revealed a tumor-specific loss of CDH3 mRNA expression, CDH3 DNA hypermethylation, and loss of distal tubular and collecting duct CDH3 protein expression in RCC. A relatively higher methylation level in tumors was associated with a loss of cell differentiation and higher clinical stage. siRNA-induced suppression of CDH3 expression modulated the invasion characteristics of tumor cells in the impedance-based real-time cellular analysis. Our results indicate that loss of CDH3 expression is common in RCC and may contribute to the pathogenesis of a subset of RCC. Further studies to reveal the mechanisms of loss of expression and its effects on the invasive behavior of renal tumor cells are required.
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spelling pubmed-106709992023-11-18 Alteration of Cadherin 3 Expression and DNA Methylation in Association with Aggressive Renal Cell Carcinoma Faraj Tabrizi, Pouriya Peters, Inga Schimansky, Inga Dubrowinskaja, Natalia Reese, Christel Tezval, Hossein Kuczyk, Markus Antonius Serth, Jürgen Int J Mol Sci Article Cadherins (calcium-dependent adhesion proteins) are important in cellular adhesion and may play a role in the development and progression of renal cell carcinoma (RCC). This study investigated changes in cadherin 3 (CDH3; P-cadherin) mRNA expression, DNA methylation, and protein expression in RCC and compared the results with the histopathological and clinical characteristics of patients. The possible contribution of CDH3 to tumor cell invasiveness was tested in a functional assay using siRNA-based suppression of CDH3 expression and subsequent real-time impedance analysis using a Matrigel invasion model. Our analyses revealed a tumor-specific loss of CDH3 mRNA expression, CDH3 DNA hypermethylation, and loss of distal tubular and collecting duct CDH3 protein expression in RCC. A relatively higher methylation level in tumors was associated with a loss of cell differentiation and higher clinical stage. siRNA-induced suppression of CDH3 expression modulated the invasion characteristics of tumor cells in the impedance-based real-time cellular analysis. Our results indicate that loss of CDH3 expression is common in RCC and may contribute to the pathogenesis of a subset of RCC. Further studies to reveal the mechanisms of loss of expression and its effects on the invasive behavior of renal tumor cells are required. MDPI 2023-11-18 /pmc/articles/PMC10670999/ /pubmed/38003666 http://dx.doi.org/10.3390/ijms242216476 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 Article
Faraj Tabrizi, Pouriya
Peters, Inga
Schimansky, Inga
Dubrowinskaja, Natalia
Reese, Christel
Tezval, Hossein
Kuczyk, Markus Antonius
Serth, Jürgen
Alteration of Cadherin 3 Expression and DNA Methylation in Association with Aggressive Renal Cell Carcinoma
title Alteration of Cadherin 3 Expression and DNA Methylation in Association with Aggressive Renal Cell Carcinoma
title_full Alteration of Cadherin 3 Expression and DNA Methylation in Association with Aggressive Renal Cell Carcinoma
title_fullStr Alteration of Cadherin 3 Expression and DNA Methylation in Association with Aggressive Renal Cell Carcinoma
title_full_unstemmed Alteration of Cadherin 3 Expression and DNA Methylation in Association with Aggressive Renal Cell Carcinoma
title_short Alteration of Cadherin 3 Expression and DNA Methylation in Association with Aggressive Renal Cell Carcinoma
title_sort alteration of cadherin 3 expression and dna methylation in association with aggressive renal cell carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10670999/
https://www.ncbi.nlm.nih.gov/pubmed/38003666
http://dx.doi.org/10.3390/ijms242216476
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