Signaling pathways involved in collagen-induced disruption of the E-cadherin complex during epithelial-mesenchymal transition

There is substantial interest in the influence of the microenvironment on tumor cells. Cell-cell as well as cell-matrix interactions have been correlated with the control of different processes such as tumor cell proliferation, differentiation, survival and migration. In this review, we focus on the influence of collagen types I and III expressed in carcinomata on the E-cadherin-mediated adhesion between epithelial tumor cells. Recently published studies described the ability of fibrillar collagen to reduce E-cadherin gene expression and to induce disruption of the E-cadherin adhesion complex. The reduced cellular adhesion influences tissue integrity and has been correlated with elevated cell migration and invasion of different carcinoma cells. Altered tyrosine phosphorylation of the intracellular, cadherin-associated catenins was identified as an important regulator of collagen-induced disassembly of the E-cadherin adhesion complex. The molecular mechanisms involved in collagen-induced cell transformation include activation of integrins, activation and translocation of the focal adhesion kinase to the E-cadherin/catenin complex as well as inhibition of the phosphatase PTEN. Copyright (c) 2007 S. Karger AG, Basel.