Cadherins and their Role in Malignant Transformation: Implications for Skin Cancer Progression

Abstract

Cadherins are a large family of Ca 2+ dependent adhesion proteins. They are transmem-brane or closely related to membrane glycoproteins localized in specialized adhesive junction. The expression of various cadherins may be concomitant with cancer progression steps and the term 'cadherin switch' has been created due to the observation of down-regulation of E-cadherin (suppressor of metastatic potential) and up-regulation of N-cadherin (promoter of metastatic potential) expression during tumour progression. These changes are thought to be closely related to epithelial-to-mesenchy-mal transition of cells of many different types of cancer including skin cancers, and accompany the increase of their motility and invasion abilities resulting in the metastasis formation. The cadherin polypeptide is a potential substrate for post-translational modification, for example, N-glycosylation, and its important role in the regulation of cadherin function has been described. The changed glycosylation of cadherins has been described in various skin cancers including melanoma and was consistent with cadherins' role in epithelial-to-mesenchymal transition. The detailed analysis of cadherin expression and cadherin-related glycosylation changes taking place during malignant transformation could be a key for better understanding of the nature of this process and may open new opportunities for the creation of more effective anticancer therapeutics and diagnostic tools.