E-cadherin—catenin cell—cell adhesion complex and human cancer

Abstract

Background: The E-cadherin–catenin complex plays a crucial role in epithelial cell–cell adhesion and in the maintenance of tissue architecture. Perturbation in the expression or function of this complex results in loss of intercellular adhesion, with possible consequent cell transformation and tumour progression. Recently, much progress has been made in understanding the interaction between the different components of this protein complex and how this cell–cell adhesion complex is modulated in cancer cells. Methods: This is an update of the role of the E-cadherin–catenin complex in human cancers. It emphasizes new features and the possible role of the complex in clinical practice, discussed in the light of 165 references obtained from the Medline database from 1995 to 1999. Results: More evidence is now appearing to suggest that disturbance in protein–protein interaction in the E-cadherin–catenin adhesion complex is one of the main events in the early and late steps of cancer development. An inverse correlation is found between expression of the E-cadherin–catenin complex and the invasive behaviour of tumour cells. Therefore, E-cadherin–catenin may become a significant prognostic marker for tumour behaviour. Besides its role in establishing tight cell–cell adhesion, β- catenin plays a major role in cell signalling and promotion of neoplastic growth. This suggests its dual role as a tumour suppressor and as an oncogene in human cancers. Conclusion: Recent developments show that the E-cadherin–catenin complex is more than a ‘sticky molecular complex’. Further studies may yield greater insight into the early molecular interactions critical to the initiation and progression of tumours. This should aid the development of novel strategies for both prevention and treatment of cancer.