epithelial-cadherin-catenin complex in human carcinomas

The ErbB family of receptor tyrosine kinases have important roles in maintaining normal epithelial cell function. The ErbBs are involved in the interaction between cells and cell–matrix adhesion molecules and have proven critical in maintaining the integrity of the epithelial cell environment. Deregulation of these tyrosine receptors has been associated with several human diseases. In particular, the expression or activation of epidermal growth factor receptor (EGFR) and ErbB2 is altered in many epithelial tumors. Epithelial (E)-cadherin is another major molecule expressed by epithelial cells. To create efficient cell–cell adhesion, E-cadherin couples its cytoplasmic domain to catenins and the actin cytoskeleton. The loss of intercellular adhesion appears to be a fundamental aspect of the neoplastic phenomena. In addition, EGFR and ErbB2 signaling associated with the E-cadherin–catenin complex has been demonstrated in normal and cancer cells. This signaling is involved in regulating cell adhesion and the invasive growth of cancers. This article provides an overview of the interaction between the ErbB tyrosine receptors and the E-cadherin–catenin complex in human carcinomas. Proper regulation of a cell depends on cell homeostasis. This regulation requires a rapid response to extracellular and intracellular signals, and is critically mediated by soluble growth factors and their trans-membrane receptors. When activated by their growth factors, the receptors simultaneously launch ‘positive signals’, which lead to cell stimulation, and ‘negative signals’, which regulate the amplitude and duration of these positive signals [1]. The correct interpretation and integration of these positive and negative signals is vital for normal cell homeostasis, and its disturbance is often implicated in disease. The ErbB family of receptor tyrosine kinases (RTKs) and their ligands, soluble factors of the epidermal growth factor (EGF) family, provide the best examples of unbalanced cell signals. Over-expressed or mutated ErbB receptors, as well as unleashed downstream effectors, lead to excessive cell proliferation and are often associated with human cancer [2]. The first study concerning the expression of EGF receptor (R) in human breast tumors and its association with poor prognosis was published 20 years ago [3]. This review focuses on ErbB-receptor signaling in normal and diseased conditions and their interaction with the (E)-cadherin–catenin complex in human carcinomas.