Please use this identifier to cite or link to this item:
http://hdl.handle.net/10773/24307
Title: | P-cadherin functional role is dependent on E-cadherin cellular context: a proof of concept using the breast cancer model |
Author: | Ribeiro, Ana Sofia Sousa, Bárbara Carreto, Laura Mendes, Nuno Nobre, Ana Rita Ricardo, Sara Albergaria, André Cameselle-Teijeiro, Jorge F. Gerhard, Rene Söderberg, Ola Seruca, Raquel Santos, Manuel A. Schmitt, Fernando Paredes, Joana |
Keywords: | E-cadherin P-cadherin breast cancer invasion motility |
Issue Date: | 2013 |
Publisher: | John Wiley and Sons |
Abstract: | P-cadherin overexpression is associated with worse breast cancer survival, being a poor prognostic marker as well as a putative therapeutic target for the aggressive triple-negative and basal-like carcinomas (TNBCs). Previously, we have shown that P-cadherin promotes breast cancer invasion of cells where membrane E-cadherin was maintained; however, it suppresses invasion in models without endogenous cadherins, like melanomas. Here, we investigated if P-cadherin expression would interfere with the normal adhesion complex and which were the cellular/molecular consequences, constituting, in this way, a new mechanism by which E-cadherin invasive-suppressor function was disrupted. Using breast TNBC models, we demonstrated, for the first time, that P-cadherin co-localizes with E-cadherin, promoting cell invasion due to the disruption caused in the interaction between E-cadherin and cytoplasmic catenins. P-cadherin also induces cell migration and survival, modifying the expression profile of cells expressing wild-type E-cadherin and contributing to alter their cellular behaviour. Additionally, E- and P-cadherin co-expressing cells significantly enhanced in vivo tumour growth, compared with cells expressing only E- or only P-cadherin. Finally, we still found that co-expression of both molecules was significantly correlated with high-grade breast carcinomas, biologically aggressive, and with poor patient survival, being a strong prognostic factor in this disease. Our results show a role for E- and P-cadherin co-expression in breast cancer progression and highlight the potential benefit of targeting P-cadherin in the aggressive tumours expressing high levels of this protein. |
Peer review: | yes |
URI: | http://hdl.handle.net/10773/24307 |
DOI: | 10.1002/path.4143 |
ISSN: | 0022-3417 |
Appears in Collections: | CESAM - Artigos DBio - Artigos |
Files in This Item:
File | Description | Size | Format | |
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Ribeiro et al. - 2013 - P-cadherin functional role is dependent on E-cadhe.pdf | 1.56 MB | Adobe PDF |
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