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Notch signaling mediates TGF-β1-induced EMT through the induction of Snai1

Matsuno, Yosuke and Coelho, Ana and Jarai, Gabor and Westwick, John and Hogaboam, Cory (2012) Notch signaling mediates TGF-β1-induced EMT through the induction of Snai1. The International Journal of Biochemistry and Cell Biology, 44 (5). pp. 776-789. ISSN 1357-2725

Abstract

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-β1-induced EMT.
Inhibition of Notch signaling either by
γ-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-β1-induced
EMT through induction of Snai1. Further
studies on Notch signaling may provide
diagnostic and therapeutic targets for cancer
and fibrotic disease.

Item Type: Article
Keywords: EMT, notch, Snai-1
Date Deposited: 13 Oct 2015 13:15
Last Modified: 13 Oct 2015 13:15
URI: https://oak.novartis.com/id/eprint/5407

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