Requirement of protein kinase Calpha, extracellular matrix remodeling, and cell-matrix interaction for transforming growth factorbeta-regulated expression of E-cadherin and catenins

J Cell Physiol. 2001 May;187(2):188-95. doi: 10.1002/jcp.1068.

Abstract

A hallmark of transforming growth factorbeta (TGFbeta) 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 TGFbeta function is not well-understood. In the epithelium-derived human colon cancer cell line Moser, TGFbeta induces extracellular-matrix remodeling in a protein kinase Calpha-dependent manner. In this study we showed that TGFbeta 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/gamma-catenin complex formation. We found that the induction of E-cadherin and alpha- and beta-catenin by TGFbeta was also dependent on protein kinase Calpha, whereas the induction of gamma-catenin was independent of protein kinase Calpha but dependent on other protein kinase C isoforms. We also found that protein kinase Calpha-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 alpha- and beta-catenin but not gamma-catenin) by TGFbeta. We therefore concluded that two signal pathways exist in TGFbeta-regulated expression of E-cadherin and the catenins. We also concluded that a functional significance of TGFbeta-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 alpha- and beta-catenin).

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cadherins / genetics*
  • Cadherins / metabolism
  • Cell Adhesion / physiology
  • Colonic Neoplasms
  • Cytoskeletal Proteins / genetics*
  • Cytoskeletal Proteins / metabolism
  • Desmoplakins
  • Extracellular Matrix / enzymology
  • Gene Expression / drug effects
  • Gene Expression / physiology
  • Humans
  • Isoenzymes / metabolism*
  • Protein Kinase C / metabolism*
  • Protein Kinase C-alpha
  • Signal Transduction / physiology
  • Trans-Activators*
  • Transforming Growth Factor beta / pharmacology*
  • Tumor Cells, Cultured / cytology
  • Tumor Cells, Cultured / enzymology
  • alpha Catenin
  • beta Catenin
  • gamma Catenin

Substances

  • CTNNA1 protein, human
  • CTNNB1 protein, human
  • Cadherins
  • Cytoskeletal Proteins
  • Desmoplakins
  • Isoenzymes
  • JUP protein, human
  • Trans-Activators
  • Transforming Growth Factor beta
  • alpha Catenin
  • beta Catenin
  • gamma Catenin
  • PRKCA protein, human
  • Protein Kinase C
  • Protein Kinase C-alpha