P-cadherin signals through the laminin receptor alpha 6 beta 4 integrin to induce stem cell and invasive properties to basal-like breast cancer cells

• Tipo: Artigo em Revista Científica Internacional
• Data: 2014

Autores

Vieira, AF (Autor) Outra; Ribeiro, AS (Autor) Outra; Dionisio, MR (Autor) Outra; Sousa, B (Autor) Outra; Nobre, AR (Autor) Outra; Albergaria, A (Autor) Outra; Santiago Gomez, A (Autor) Outra; Mendes, N (Autor) Outra; Gerhard, R (Autor) Outra; Fernando Schmitt (Autor) FMUP; Clarke, RB (Autor) Outra; Paredes, J (Autor) Outra

Revista

Título: Oncotarget

Vol. 5

Páginas: 679-692

ISSN: 1949-2553

Editora: Impact Journals

Indexação

ISI Web of Knowledge - 46 Citações

Scopus - 46 Citações

Outras Informações

ID Authenticus: P-009-KQ1

Abstract (EN): P-cadherin is a classical cell-cell adhesion molecule that, in contrast to E-cadherin, has a positive role in breast cancer progression, being considered a poor prognostic factor in this disease. In previous reports, we have shown that this protein induces cancer stem cell and invasive properties to basal-like breast cancer cells. Here, we clarify the downstream signaling pathways that are triggered by P-cadherin to mediate these effects. We demonstrated that P-cadherin inhibition led to a significant decreased adhesion of cancer cells to the basement membrane substrate laminin, as well as to a major reduction in the expression of the laminin receptor alpha 6 beta 4 integrin. Remarkably, the expression of this heterodimer was required for the invasive capacity and increased mammosphere forming efficiency induced by P-cadherin expression. Moreover, we showed that P-cadherin transcriptionally up-regulates the alpha 6 integrin subunit expression and directly interacts with the beta 4 integrin subunit. We still showed that P-cadherin downstream signaling, in response to laminin, involves the activation of focal adhesion (FAK), Src and AKT kinases. The association between the expression of P-cadherin, alpha 6 beta 4 heterodimer and the active FAK and Src phosphorylated forms was validated in vivo. Our data establish that there is a crosstalk between P-cadherin and the laminin receptor alpha 6 beta 4 integrin signaling pathway, which link has never been previously described. The activation of this heterodimer explains the stem cell and invasive properties induced by P-cadherin to breast cancer cells, pointing to a new molecular mechanism that may be targeted to counteract the effects induced by this adhesion molecule.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 14