Nutlin-3 inhibits epithelial-mesenchymal transition by interfering with canonical transforming growth factor-尾1-Smad-Snail/Slug axis

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• 作者：Yeping Wu ; Yingying Fu ; Lin Zheng ; Guanyu Lin ; Jian Ma ; Jianshu Lou ; Hong Zhu ; Qiaojun He ; Bo Yang
• 关键词：TGF-尾1 ; EMT ; Nutlin-3 ; Smad pathway
• 刊名：Cancer Letters
• 出版年：1 January, 2014
• 年：2014
• 卷：342
• 期：1
• 页码：82-91
• 全文大小：2169 K

文摘

Enormous efforts have been made to explore small molecules that interfere with the TGF-尾 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-尾1 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-尾1-Smad-Snail/Slug axis, in a p53-independent manner.