Integrin-linked kinase function is required for transforming growth factor beta-mediated epithelial to mesenchymal transition.
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.
Lee
Yoon-Ik
YI
Laboratory of Visual Sciences, Korea Eye Tissue and Gene Bank, College of Medicine, The Catholic University of Korea, Catholic Research Institutes of Medicine Science, Seoul 137-040, Republic of Korea.
Kwon
Yeon-Jin
YJ
Joo
Choun-Ki
CK
D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D004848:Epithelium / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D008648:Mesoderm / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013329:Structure-Activity Relationship; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D000099200:Scaffold Protein ILK
D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D000099200:Scaffold Protein ILK; C494918:AKT1 protein, human