Requirement of protein kinase Cα, extracellular matrix remodeling, and cell–matrix interaction for transforming growth factorβ‐regulated expression of E‐cadherin and catenins

Publisher Website
Google Scholar
Abstract
A hallmark of transforming growth factorβ (TGFβ) action is the induction of the synthesis and secretion of extracellular‐matrix adhesion molecules and induction of the cell‐surface expression of integrin receptors for these molecules (termed extracellular‐matrix remodeling). The signal pathways leading to extracellular‐matrix remodeling and the significance of extracellular‐matrix remodeling in TGFβ function is not well‐understood. In the epithelium‐derived human colon cancer cell line Moser, TGFβ induces extracellular‐matrix remodeling in a protein kinase Cα‐dependent manner. In this study we showed that TGFβ was a potent inducer of the homotypic cell–cell adhesion molecule E‐cadherin and its undercoat‐associated proteins, the catenins and dramatically increased the amount of E‐cadherin/γ‐catenin complex formation. We found that the induction of E‐cadherin and α‐ and β‐catenin by TGFβ was also dependent on protein kinase Cα, whereas the induction of γ‐catenin was independent of protein kinase Cα but dependent on other protein kinase C isoforms. We also found that protein kinase Cα‐dependent induction of extracellular‐matrix remodeling and subsequent cell–matrix interaction requiring both fibronectin and laminin were a prerequisite for the induction of E‐cadherin (and α‐ and β‐catenin but not γ‐catenin) by TGFβ. We therefore concluded that two signal pathways exist in TGFβ‐regulated expression of E‐cadherin and the catenins. We also concluded that a functional significance of TGFβ‐induced extracellular matrix remodeling is the activation of signal transduction mechanisms through increased interaction between extracellular matrix fibronectin and laminin and their cell‐surface integrin receptors, which lead to the induction of E‐cadherin (and α‐ and β‐catenin).