Integrin-linked kinase function is required for transforming growth factor beta-mediated epithelial to mesenchymal transition

Biochem Biophys Res Commun. 2004 Apr 16;316(4):997-1001. doi: 10.1016/j.bbrc.2004.02.150.


The role of integrin-linked kinase (ILK) in transforming growth factor beta (TGFbeta)-mediated epithelial to mesenchymal transition was investigated. A stable transfection of dominant-negative ILK results in the prevention of TGFbeta-mediated E-cadherin delocalization. TGFbeta-mediated phosphorylation of Akt at Ser-473 was inhibited by dominant-negative ILK and PI3K inhibitors, LY294002 and wortmannin. Treatment with TGFbeta stimulated induction of Akt and ILK kinase activity in HaCat control cells. This increased ILK activity by TGFbeta was lowered by PI3K inhibitor, LY294002. In addition, PI3K inhibitor, dominant-negative Akt, and dominant-negative ILK could not block TGFbeta-mediated C-terminal phosphorylation of Smad2. Taken together, these data suggest that PI3K-ILK-Akt pathway that is independent of the TGFbeta-induced Smad pathway is required for TGFbeta-mediated epithelial to mesenchymal transition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation / physiology*
  • Cells, Cultured
  • Epithelium / metabolism*
  • Epithelium / ultrastructure
  • Humans
  • Keratinocytes / cytology
  • Keratinocytes / metabolism*
  • Mesoderm / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-akt
  • Recombinant Proteins / metabolism
  • Signal Transduction / physiology*
  • Structure-Activity Relationship
  • Transfection
  • Transforming Growth Factor beta / metabolism*


  • Proto-Oncogene Proteins
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • integrin-linked kinase
  • AKT1 protein, human
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt