Notch signaling mediates TGF-β1-induced epithelial-mesenchymal transition through the induction of Snail

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-beta 1-induced EMT. Inhibition of Notch signaling either by gamma-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 Snail expression via direct transcriptional activation. Collectively, these data show that Notch signaling activation promote TGF-beta 1-induced EMT through the induction of Snai1. Further studies on Notch signaling may provide diagnostic and therapeutic targets for cancer and fibrotic disease. (c) 2012 Elsevier Ltd. All rights reserved.