Co-expression of E- and P-cadherin in breast cancer: role as an invasion suppressor or as an invasion promoter?

Cadherins are cell-cell adhesion molecules. During tumor progression, their expression and/or function are frequently altered. E-cadherin down-regulation is often associated with tumor initiation and progression in breast cancer [1], whereas P-cadherin overexpression is associated with a worse patient survival [2] and with invasive breast cancer cells [3].

In this study, we aimed to understand if P-cadherin overexpression could interfere with E-cadherin invasion suppressor role in breast cancer.

Therefore, E- and P-cadherin expression was evaluated in a series of invasive breast carcinomas. P-cadherin overexpressing tumors often do not loose E-cadherin and tumors co-expressing both cadherins showed a more aggressive behavior and were related with the worst patient survival. Further, we performed in vitro studies by silencing both cadherins in BT-20 breast cancer cells. E- and P-cadherin co-expressing breast cancer cells showed increased cell invasion and migration capacities, when compared with the ones expressing only one cadherin. P-cadherin silencing led to increased levels of cell death, demonstrating it as a cancer cell survival signal. Also, microarrays of BT-20 cells, after E- and/or P-cadherin silencing, showed that the role of each cadherin alone is distinct from when these are co-expressed in the same cell, conferring different transcriptional programs.

We can conclude that E- and P-cadherin co-expression has an invasion promoter role in breast cancer cells and is a poor patient prognostic biomarker.