Transforming growth factor β regulates cell–cell adhesion through extracellular matrix remodeling and activation of focal adhesion kinase in human colon carcinoma Moser cells

Abstract

Transforming growth factor (TGF) is a potent regulator of cell–matrix and cell-cell adhesions (collectively termed cellular adhesions). Cellular adhesions play crucial roles in controlling the differentiation of epithelial cells and in maintaining the integrity of the epithelium. Loss of TGF -responsiveness is thought to be an important early initiating event in the malignant progression of epithelial cancer. In the TGF-responsive human colon adenocarcinoma Moser cells, TGF promotes cellular adhesions and suppresses their malignant phenotype. TGF promotes cell–matrix adhesion by inducing the synthesis of extracellular matrix (ECM) adhesion molecules and the expression of integrin receptors for these molecules (termed ECM remodeling). TGF promotes cell–cell adhesion through the induction of E-cadherin expression, an epithelial associated homotypic cell–cell adhesion molecule, which also functions as a tumor suppressor in colon cancer. How TGF regulates E-cadherin expression is not known. In this study, we showed that the induction of E-cadherin by TGF was mediated through the activation of focal adhesion kinase (FAK), a major signaling molecule in focal adhesion contacts and that the activation of FAK was due to ECM remodeling and increased cell–matrix interactions. Thus, TGF regulates cell–cell adhesion through its ability to remodel the ECM and to activate FAK through ECM remodeling.