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Pro-Tumorigenic Phosphorylation of p120 Catenin in Renal and Breast Cancer
Altered protein expression and phosphorylation are common events during malignant transformation. These perturbations have been widely explored in the context of E-cadherin cell-cell adhesion complexes, which are central in the maintenance of the normal epithelial phenotype. A major component of the...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4466266/ https://www.ncbi.nlm.nih.gov/pubmed/26067913 http://dx.doi.org/10.1371/journal.pone.0129964 |
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author | Kourtidis, Antonis Yanagisawa, Masahiro Huveldt, Deborah Copland, John A. Anastasiadis, Panos Z. |
author_facet | Kourtidis, Antonis Yanagisawa, Masahiro Huveldt, Deborah Copland, John A. Anastasiadis, Panos Z. |
author_sort | Kourtidis, Antonis |
collection | PubMed |
description | Altered protein expression and phosphorylation are common events during malignant transformation. These perturbations have been widely explored in the context of E-cadherin cell-cell adhesion complexes, which are central in the maintenance of the normal epithelial phenotype. A major component of these complexes is p120 catenin (p120), which binds and stabilizes E-cadherin to promote its adhesive and tumor suppressing function. However, p120 is also an essential mediator of pro-tumorigenic signals driven by oncogenes, such as Src, and can be phosphorylated at multiple sites. Although alterations in p120 expression have been extensively studied by immunohistochemistry (IHC) in the context of tumor progression, little is known about the status and role of p120 phosphorylation in cancer. Here we show that tyrosine and threonine phosphorylation of p120 in two sites, Y228 and T916, is elevated in renal and breast tumor tissue samples. We also show that tyrosine phosphorylation of p120 at its N-terminus, including at the Y228 site is required for its pro-tumorigenic potential. In contrast, phosphorylation of p120 at T916 does not affect this p120 function. However, phosphorylation of p120 at T916 interferes with epitope recognition of the most commonly used p120 antibody, namely pp120. As a result, this antibody selectively underrepresents p120 levels in tumor tissues, where p120 is phosphorylated. Overall, our data support a role of p120 phosphorylation as a marker and mediator of tumor transformation. Importantly, they also argue that the level and localization of p120 in human cancer tissues immunostained with pp120 needs to be re-evaluated. |
format | Online Article Text |
id | pubmed-4466266 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-44662662015-06-25 Pro-Tumorigenic Phosphorylation of p120 Catenin in Renal and Breast Cancer Kourtidis, Antonis Yanagisawa, Masahiro Huveldt, Deborah Copland, John A. Anastasiadis, Panos Z. PLoS One Research Article Altered protein expression and phosphorylation are common events during malignant transformation. These perturbations have been widely explored in the context of E-cadherin cell-cell adhesion complexes, which are central in the maintenance of the normal epithelial phenotype. A major component of these complexes is p120 catenin (p120), which binds and stabilizes E-cadherin to promote its adhesive and tumor suppressing function. However, p120 is also an essential mediator of pro-tumorigenic signals driven by oncogenes, such as Src, and can be phosphorylated at multiple sites. Although alterations in p120 expression have been extensively studied by immunohistochemistry (IHC) in the context of tumor progression, little is known about the status and role of p120 phosphorylation in cancer. Here we show that tyrosine and threonine phosphorylation of p120 in two sites, Y228 and T916, is elevated in renal and breast tumor tissue samples. We also show that tyrosine phosphorylation of p120 at its N-terminus, including at the Y228 site is required for its pro-tumorigenic potential. In contrast, phosphorylation of p120 at T916 does not affect this p120 function. However, phosphorylation of p120 at T916 interferes with epitope recognition of the most commonly used p120 antibody, namely pp120. As a result, this antibody selectively underrepresents p120 levels in tumor tissues, where p120 is phosphorylated. Overall, our data support a role of p120 phosphorylation as a marker and mediator of tumor transformation. Importantly, they also argue that the level and localization of p120 in human cancer tissues immunostained with pp120 needs to be re-evaluated. Public Library of Science 2015-06-11 /pmc/articles/PMC4466266/ /pubmed/26067913 http://dx.doi.org/10.1371/journal.pone.0129964 Text en © 2015 Kourtidis et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Kourtidis, Antonis Yanagisawa, Masahiro Huveldt, Deborah Copland, John A. Anastasiadis, Panos Z. Pro-Tumorigenic Phosphorylation of p120 Catenin in Renal and Breast Cancer |
title | Pro-Tumorigenic Phosphorylation of p120 Catenin in Renal and Breast Cancer |
title_full | Pro-Tumorigenic Phosphorylation of p120 Catenin in Renal and Breast Cancer |
title_fullStr | Pro-Tumorigenic Phosphorylation of p120 Catenin in Renal and Breast Cancer |
title_full_unstemmed | Pro-Tumorigenic Phosphorylation of p120 Catenin in Renal and Breast Cancer |
title_short | Pro-Tumorigenic Phosphorylation of p120 Catenin in Renal and Breast Cancer |
title_sort | pro-tumorigenic phosphorylation of p120 catenin in renal and breast cancer |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4466266/ https://www.ncbi.nlm.nih.gov/pubmed/26067913 http://dx.doi.org/10.1371/journal.pone.0129964 |
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