Involvement of members of the cadherin superfamily in cancer.

Abstract

We review the role of cadherins and cadherin-related proteins in human cancer. Cellular and animal models for human cancer are also dealt with whenever appropriate. E-cadherin is the prototype of the large cadherin superfamily and is renowned for its potent malignancy suppressing activity. Different mechanisms for inactivating E-cadherin/CDH1 have been identified in human cancers: inherited and somatic mutations, aberrant protein processing, increased promoter methylation, and induction of transcriptional repressors such as Snail and ZEB family members. The latter induce epithelial mesenchymal transition, which is also associated with induction of "mesenchymal" cadherins, a hallmark of tumor progression. VE-cadherin/CDH5 plays a role in tumor-associated angiogenesis. The atypical T-cadherin/CDH13 is often silenced in cancer cells but up-regulated in tumor vasculature. The review also covers the status of protocadherins and several other cadherin-related molecules in human cancer. Perspectives for emerging cadherin-related anticancer therapies are given.