The integrity of cell-cell adhesion in tissues partly depends on the presence of homophilic interactions of cadherins and their cytoplasmic association with the catenin complex. New structural and mutagenesis data have provided more information on the cis- and trans-mechanisms of E-cadherin dimerization and homotypic interactions. In epithelial cancer cells, cascade signaling for tumorgenesis and metastasis is initiated  subsequent to the loss of E-cadherin  function and the accumulation of cytosolic β-catenin. Controlling the E-cadherin functions and intracellular signaling network may lead to potential therapeutic applications in improving drug delivery and for drug delivery and inhibiting  tumor metastasis and invasion.