Snail is required for transforming growth factor-β-induced epithelial–mesenchymal transition by activating PI3 kinase/Akt signal pathway

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• 作者：Hee Jun Cho ; Kyoung Eun Baek ; Shizuya Saika ; Moon-Jin Jeong ; Jiyun Yoo
• 关键词：Transforming growth factor-β ; Epithelial– ; mesenchymal transition ; Snail ; PI3 kinase ; Akt
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2007
• 出版时间：9 February 2007
• 年：2007
• 卷：353
• 期：2
• 页码：337-343
• 全文大小：1979 K

文摘

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-β 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-β-induced EMT in lens epithelial cells by showing that LY294002, an inhibitor of the p110 catalytic subunit of PI3K, blocked the expression of α-smooth muscle actin (α-SMA) and morphological changes. We also identify Snail as an effector of TGF-β-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-β and the proximal Snail promoter is activated by TGF-β through the action of Smad2, 3, and 4. We show that antisense inhibition of Snail expression blocks TGF-β-induced EMT and furthermore Akt activation. All of these findings suggest that Snail participates in TGF-β-induced EMT by acting upstream of Akt activation.