During development, E-cadherin expression is under strict spatiotemporal control and downregulation is essential for certain morphogenic movements within the embryo, many of which involve epithelial-mesenchymal transition (EMT). These phenotypic transitions are reminiscent of those taking place during the acquisition of an invasive phenotype in tumors of epithelial origin. Indeed, loss of E-cadherin is involved in invasion of epithelial cells and higher migratory potential. Furthermore, perturbation in E-cadherin's interaction with the catenin/cytoskeleton complex has been associated with loss of adhesion and increased migration. The central hypothesis of this proposal is that E-cadherin mediated signaling events and interactions of E-cadherin and p120-catenin combined play a central role in the regulation of adhesion, thereby establishing a platform for eventual squamous cancer progression and metastasis. Therefore, we propose to investigate the following aims: Specific Aim 1: How do E-cadherin and p120-catenin regulate cell adhesion? Specific Aim 2: Which signal transduction pathway(s) does E-cadheirn regulate to modulate cell adhesion?