Cadherin and catenin alterations in human cancer.
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 alpha-catenin. Although there is much evidence that beta-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 beta-catenin itself, the principal consequences of beta-catenin deregulation in cancer appear to be largely distinct from the effects attributable to inactivation of E-cadherin or alpha-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.
Hajra
Karen M
KM
Program in Cellular and Molecular Biology, University of Michigan Medical School, Ann Arbor, MI 48109-0638, USA.
Fearon
Eric R
ER
D015820:Cadherins / Q000235:genetics* / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D018095:Germ-Line Mutation / Q000235:genetics / Q000502:physiology; D006801:Humans; D009154:Mutation / Q000235:genetics* / Q000502:physiology; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics*; D015534:Trans-Activators; D051176:beta Catenin
C415580:CDH19 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin