Abstract
P-cadherin is frequently over-expressed in high-grade invasive breast carcinomas and has been reported to be an enhancer of migration and invasion of breast cancer cells, being correlated with tumour aggressiveness. In addition, expression of P-cadherin is well established as an indicator of poor prognosis in human breast cancer, which has stimulated our interest in studying its role in this setting. This review describes the most important findings on P-cadherin expression and function in normal mammary tissue and breast cancer cells, emphasizing that further research is required to elucidate the role played by this protein in human mammary tumours.
Highlights
Classical cadherins, such as E-cadherin, N-cadherin and Pcadherin, are the best characterized subgroup of adhesion proteins; they mediate calcium-dependent cell-cell bonds when they are localized to the adherens-type junctions
We showed that P-cadherin expression in canine malignant tumours was significantly related to spindle cell carcinoma, carcinosarcoma and osteosarcoma
We suggested that a related mechanism could account for the induction of invasion by P-cadherin, in which destabilization of antiinvasive cadherin/catenin complexes would result from competition for the available p120-catenin
Summary
Classical cadherins, such as E-cadherin, N-cadherin and Pcadherin, are the best characterized subgroup of adhesion proteins; they mediate calcium-dependent cell-cell bonds when they are localized to the adherens-type junctions. These findings support the hypothesis that there is a common histogenesis for both elements from stem cells, with the capacity for divergent differentiation, as suggested by several studies on human and canine mammary tumours [76], but more data are needed to clarify this issue These specific types of P-cadherin positive carcinomas appear to have a myoepithelial/basal-like transcriptomic programme, this explanation is unlikely to account for the percentage of P-cadherin expressing ductal carcinomas. Aberrant epithelial P-cadherin expression is associated with a proliferative and undifferentiated cell phenotype related to ulceration and neoplastic transformation, the relative functional role played by P-cadherin in breast cancer cell invasion and motility is not fully elucidated [87] This is due in part to results obtained with transgenic mice expressing high levels of P-cadherin in the normal mammary epithelium that did not develop tumours, even when neu oncogene induced mammary tumours were produced, giving rise to consistently P-cadherin negative lesions [32].
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