Our research focuses on the cell adhesion molecule, E-cadherin. Cell migration and metastasis are often associated with loss of E-cadherin and reduced E-cadherin expression has been associated with unfavorable patient prognosis. More than 50% of patients diagnosed with esophageal cancer, which we study, have unresectable or metastatic disease at the time of presentation. The role of E-cadherin in maintenance of cell adhesion and preservation of the epithelial phenotype is well known, however, its effect on cell signal transduction is less characterized. We have previously shown that 70% of esophageal squamous cell carcinoma demonstrate the coordinated loss of E-cadherin and TGFb receptor II (TbRII). To model E-cadherin and TbRII loss in vitro, we established organotypic cultures which mimic the tumor microenvironment. These cultures allow the analysis of the cross-talk between epithelial and stromal cells as well as the identifcation of signaling pathways modulated during invasion and metastasis. Based in this model we analyze the Activin signlaing pathway and its role in inducing epithelial cell invasion as wel as activating the surrounding stroma (fibroblasts). We further utilize animal models to study tumor progression in vivo and investigate aspects of crosstalk of the epithelial compartment with the tumor microenvironment. Animals with double knock-out of E-cadherin and TGFb receptor II develop squamous head-and-neck cancer. In vitro and in vivo models are also the basis for projects relating to the role of miRNAs in esophageal cancer.