Snail is required for transforming growth factor-beta-induced epithelial-mesenchymal transition by activating PI3 kinase/Akt signal pathway.
Lens epithelial cells undergo epithelial-mesenchymal transition (EMT) after injury as in cataract extraction, leading to fibrosis of the lens capsule. We have previously shown that EMT of primary lens epithelial cells in vitro depends on TGF-beta expression and more specifically, on signaling via Smad3. In this report, we suggest phosphatidylinositol 3-OH kinase (PI3K)/Akt signaling is also necessary for TGF-beta-induced EMT in lens epithelial cells by showing that LY294002, an inhibitor of the p110 catalytic subunit of PI3K, blocked the expression of alpha-smooth muscle actin (alpha-SMA) and morphological changes. We also identify Snail as an effector of TGF-beta-induced EMT. Snail has been shown to be a mediator of EMT during metastasis of cancer. We show that Snail is an immediate-early response gene for TGF-beta and the proximal Snail promoter is activated by TGF-beta through the action of Smad2, 3, and 4. We show that antisense inhibition of Snail expression blocks TGF-beta-induced EMT and furthermore Akt activation. All of these findings suggest that Snail participates in TGF-beta-induced EMT by acting upstream of Akt activation.
Cho
Hee Jun
HJ
Department of Microbiology/Research Institute of Life Science, Gyeongsang National University, Jinju 660-701, Republic of Korea.
Baek
Kyoung Eun
KE
Saika
Shizuya
S
Jeong
Moon-Jin
MJ
Yoo
Jiyun
J
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D007908:Lens, Crystalline / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008648:Mesoderm / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000008:administration & dosage*
D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt