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P‐cadherin functional role is dependent on E‐cadherin cellular context: a proof of concept using the breast cancer model
Author(s) -
Ribeiro Ana Sofia,
Sousa Bárbara,
Carreto Laura,
Mendes Nuno,
Nobre Ana Rita,
Ricardo Sara,
Albergaria André,
CameselleTeijeiro Jorge F,
Gerhard Rene,
Söderberg Ola,
Seruca Raquel,
Santos Manuel A,
Schmitt Fernando,
Paredes Joana
Publication year - 2013
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.4143
Subject(s) - cadherin , catenin , cancer research , breast cancer , biology , context (archaeology) , cell adhesion molecule , cancer , cell , microbiology and biotechnology , signal transduction , wnt signaling pathway , genetics , paleontology
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. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.