The E-cadherin/epidermal growth factor receptor interaction: A hypothesis of reciprocal and reversible control of intercellular adhesion and cell proliferation

The E-cadherin/catenin complex is a calcium-dependent cell-cell adhesion molecule, whose function is critical to the integrity of the adherens junction and which plays a role in the establishment and maintenance of normal epithelial morphology and differentiation. Loss of E-cadherin-mediated adhesion appears to be a fundamental aspect of the neoplastic phenotype which in some cases appears to be mediated by post-translational modifications (i.e. tyrosine phosphorylation) of its interacting proteins, the catenins which link E-cadherin to the actin cytoskeleton. There is increasing experimental evidence to suggest that epidermal growth factor receptor tyrosine phosphorylation may lead to the inactivation of the E- cadherin/catenin complex in cancer cells through its interaction with β- or γ-catenin in the cytoskeleton. Modulation of epidermal growth factor receptor activity by pharmacological agents has the potential to regulate a variety of cellular processes including adhesion, differentiation, and proliferation.