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Updated: May 8, 2026

Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
Nutlin-3 inhibits epithelial-mesenchymal transition by interfering with canonical transforming growth
Yeping Wu1, Yingying Fu, Lin Zheng
1Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Abstract:
Enormous efforts have been made to explore small molecules that interfere with the TGF-β signaling pathway, so as to inhibit EMT and the cancer metastasis, but few agents have been identified. In this study, we demonstrated that Nutlin-3 could abolish the down-regulation of E-cadherin induced by TGF-β1 in p53-deficient cancer cells. Further studies revealed that Nutlin-3 prohibited EMT by blocking the phosphorylation of Smad2/3, resulting in the decreased transcription of Snail/Slug. In addition, Nutlin-3 suppressed the motility of cancer cells, and potentiated the anti-proliferative activity of gefitinib and lapatinib. Collectively, Nutlin-3 could inhibit EMT and enhance the anti-cancer activity of EGFR inhibitors by interfering with the canonical TGF-β1-Smad-Snail/Slug axis, in a p53-independent manner.
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