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 Β-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.