P-cadherin is a cell-
cell adhesion molecule, whose expression is highly associated with undifferentiated cells in normal adult epithelial tissues, as well as with poorly differentiated
carcinomas. Its expression has been already reported in human embryonic stem cells and it is presumed to be a marker of stem or progenitor cells of some epithelial tissues. In normal breast,
P-cadherin has an essential role during ductal mammary branching, being expressed by the monolayer of epithelial cap cells at the end buds. In mature mammary tissue, its expression is restricted to the myoepithelium; it has been postulated that it may also be present in early
luminal progenitor cells. In
breast cancer,
P-cadherin is frequently overexpressed in high-grade tumours, being a well-established
indicator of poor patient prognosis. It has been reported as an important inducer of
cancer cell migration and invasion, with underlying molecular mechanisms involving the signalling mediated by its juxtamembrane domain, the secretion of matrix
metalloproteases to the extracellular media, and the cleavage of a
P-cadherin soluble form with pro-invasive activity. Intracellularly, this
protein interferes with the endogenous
cadherin/
catenin complex, inducing
p120-catenin delocalization to the cytoplasm, and the consequent activation of Rac1/Cdc42 and associated alterations in the actin cytoskeleton. Considering
P-cadherin's role in
cancer cell invasion and
metastasis formation, a humanized
monoclonal antibody was recently produced to antagonize
P-cadherin-associated signalling pathways, which is currently under Phase I clinical trials. In this review, the most important findings about the role of
P-cadherin in normal breast development and
cancer will be illustrated and discussed, with emphasis on the most recent data.