Cadherin and catenin alterations in human cancer

Abstract

Among the hallmarks of cancer are defective cell-cell and cell-matrix adhesion. Alterations in cadherin-catenin complexes likely have a major contributing role in cell-adhesion defects in carcinomas arising in many different tissues. E-cadherin, the prototypic member of the cadherin transmembrane protein family, regulates cell adhesion by interacting with E-cadherin molecules on opposing cell surfaces. E-cadherin's function in cell adhesion is also critically dependent on its ability to interact through its cytoplasmic domain with catenin proteins. A diverse collection of defects alter cadherin-catenin function in cancer cells, including loss-of-function mutations and defects in the expression of E-cadherin and certain catenins, such as α-catenin. Although there is much evidence that β-catenin is deregulated in cancer as a result of inactivating mutations in the APC and AXIN tumor-suppressor proteins and gain-of-function mutations in β-catenin itself, the principal consequences of α-catenin deregulation in cancer appear to be largely distinct from the effects attributable to inactivation of E-cadherin or α-catenin. In this review, we highlight some of the specific genetic and epigenetic defects responsible for altered cadherin and catenin function in cancer, as well as potential contributions of cadherin-catenin alterations to the cancer process. © 2002 Wiley-Liss, Inc.