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.
journal_name
Cancer Lettjournal_title
Cancer lettersauthors
Wu Y,Fu Y,Zheng L,Lin G,Ma J,Lou J,Zhu H,He Q,Yang Bdoi
10.1016/j.canlet.2013.08.039subject
Has Abstractpub_date
2014-01-01 00:00:00pages
82-91issue
1eissn
0304-3835issn
1872-7980pii
S0304-3835(13)00624-1journal_volume
342pub_type
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