P-cadherin functional role is dependent on E-cadherin cellular context : a proof of concept using the breast cancer model

摘要: P-cadherin overexpression is associated with worse breast cancer survival, being a poor prognostic marker as well putative therapeutic target for the aggressive triple-negative and basal-like carcinomas (TNBCs). Previously, we have shown that promotes invasion of cells where membrane E-cadherin was maintained; however, it suppresses in models without endogenous cadherins, like melanomas. Here, investigated if expression would interfere normal adhesion complex which were cellular/molecular consequences, constituting, this way, new mechanism by invasive-suppressor function disrupted. Using TNBC models, demonstrated, first time, co-localizes E-cadherin, promoting cell due to disruption caused interaction between cytoplasmic catenins. also induces migration modifying profile expressing wild-type contributing alter their cellular behaviour. Additionally, E- co-expressing significantly enhanced vivo tumour growth, compared only or P-cadherin. Finally, still found co-expression both molecules correlated high-grade carcinomas, biologically aggressive, patient strong factor disease. Our results show role progression highlight potential benefit targeting tumours high levels protein.