Cell contacts, differentiation, and invasiveness of epithelial cells

Histotypic differentiation and prognosis of carcinomas are intimately linked phemonena, i.e. poorly differentiated tumors show increased invasiveness and have a worse prognosis compared to well-differentiated tumors. In poorly differentiated carcinomas, loss of epithelial cell contacts is frequently observed; this allows the cells to break away from the primary tumor and invade surrounding tissue. The molecular basis for the disturbance of epithelial junction formation in tumors has been the subject of recent research. It has become clear that the epithelial cell adhesion molecule E-cadherin and its associated proteins, the catenins, are of central importance for the establishment of the epithelial phenotype and the prevention of invasiveness, and that aberrations in these components contribute to metastasis. The molecular mechanisms controlling the E-cadherin-based adhesion system in normal epithelial cells and in invasive carcinomas are the topic of this review.