Notch signaling mediates TGF-尾1-induced epithelial-mesenchymal transition through the induction of Snai1

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• 作者：Yosuke Matsuno^a ; ^{yosukem@umich.edu} ; Ana Lucia Coelho^a ; Gabor Jarai^b ; John Westwick^b ; Cory M. Hogaboam^a
• 关键词：EMT ; epithelial&ndash ; mesenchymal transition ; TGF ; tumor growth factor ; NICD ; notch intracellular domain ; GSI ; 纬-secretase inhibitor
• 刊名：The International Journal of Biochemistry and Cell Biology
• 出版年：2012
• 期刊代码：127_13572725
• 类别：med
• 出版时间：May, 2012
• 卷：44
• 期：5
• 页码：776-789
• 文件大小：2226 K

摘要

Epithelial-mesenchymal transition (EMT) is a process by which epithelial cells undergo phenotypic transition to mesenchymal cells and thus is involved in the pathogenesis of tumor metastasis and organ fibrosis. Notch signaling is a highly conserved pathway that regulates intercellular communication and directs cell fate decisions. Here, we show the critical role of Notch signaling in TGF-尾1-induced EMT. Inhibition of Notch signaling either by 纬-secretase inhibitor or by knocking down of Notch signaling molecules by small interfering RNA abrogated EMT in association with decreased expression of Snai1. Constitutive activation of Notch signaling was sufficient for the induction of Snai1 as well as Notch ligand Jagged1. Notch signaling induced Snai1 expression via direct transcriptional activation. Collectively, these data show that Notch signaling activation promote TGF-尾1-induced EMT through the induction of Snai1. Further studies on Notch signaling may provide diagnostic and therapeutic targets for cancer and fibrotic disease.