Extracellular cleavage and shedding of P-cadherin: a mechanism underlying the invasive behaviour of breast cancer cells

Abstract

Cell-cell adhesion is an elementary process in normal epithelial cellular architecture. Several studies have shown the role mediated by cadherins in this process, besides their role in the maintenance of cell polarity, differentiation and cell growth. However, during tumour progression, these molecules are frequently altered. In breast cancer, tumours that overexpress P-cadherin usually present a high histological grade, show decreased cell polarity and are associated with worse patient survival. However, little is known about how this protein dictates the very aggressive behaviour of these tumours. To achieve this goal, we set up two breast cancer cell models, where P-cadherin expression was differently modulated and analysed in terms of cell invasion, motility and migration. We show that P-cadherin overexpression, in breast cancer cells with wild-type E-cadherin, promotes cell invasion, motility and migration. Moreover, we found that the overexpression of P-cadherin induces the secretion of matrix metalloproteases, specifically MMP-1 and MMP-2, which then lead to P-cadherin ectodomain cleavage. Further, we showed that soluble P-cadherin fragment is able to induce in vitro invasion of breast cancer cells. Overall, our results contribute to elucidate the mechanism underlying the invasive behaviour of P-cadherin expressing breast tumours.

Integrative Analysis of Head and Neck Cancer Identifies Two Biologically Distinct HPV and Three Non-HPV Subtypes

“…2B and Supplementary Fig. S3A) similar to basal breast cancer (20). Moreover, a published EMT signature also demonstrates the elevated epithelial pathway activities in the basal subtype ( Fig.…”

Chromosomal, epigenetic and microRNA-mediated inactivation of LRP1B, a modulator of the extracellular environment of thyroid cancer cells

“…The level of gelatinases was determined as described by others (Ribeiro et al, 2010) in 24-h conditioned medium derived from 2.5 Â 10 5 cells seeded onto six-well plates previously coated with 20 mg/ml fibronectin. The experiment was performed in triplicates (three wells for each condition) and was repeated twice.…”

P-cadherin expression as a prognostic biomarker in a 3992 case tissue microarray series of breast cancer

“…In luminal MCF-7 breast cancer cells with wild-type E-cadherin, P-cadherin overexpression promoted cell invasion, motility and migration, and siRNA knockdown of P-cadherin significantly reduced the invasive potential of BT-20 cells. 73 By contrast, induction of P-cadherin in mesenchymal MDA-MB-231 cells increased aggregation and induced a partial switch from fibroblastic to epithelial morphology. 74 Loss of E-cadherinmediated cell adhesion is thought to account for the characteristic dyscohesion of tumor cells and the single file infiltration pattern of invasive lobular carcinoma.…”