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Nutlin-3 inhibits epithelial–mesenchymal transition by interfering with canonical transforming growth factor-β1-Smad-Snail/Slug axis

Authors
Journal
Cancer Letters
0304-3835
Publisher
Elsevier
Publication Date
Volume
342
Issue
1
Identifiers
DOI: 10.1016/j.canlet.2013.08.039
Keywords
  • Tgf-β1
  • Emt
  • Nutlin-3
  • Smad Pathway

Abstract

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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