作者
Philip A Gregory, Cameron P Bracken, Eric Smith, Andrew G Bert, Josephine A Wright, Suraya Roslan, Melanie Morris, Leila Wyatt, Gelareh Farshid, Yat-Yuen Lim, Geoffrey J Lindeman, M Frances Shannon, Paul A Drew, Yeesim Khew-Goodall, Gregory J Goodall
发表日期
2011/5/15
期刊
Molecular biology of the cell
卷号
22
期号
10
页码范围
1686-1698
出版商
The American Society for Cell Biology
简介
 Epithelial-mesenchymal transition (EMT) is a form of cellular plasticity that is critical for embryonic development and tumor metastasis. A double-negative feedback loop involving the miR-200 family and ZEB (zinc finger E-box-binding homeobox) transcription factors has been postulated to control the balance between epithelial and mesenchymal states. Here we demonstrate using the epithelial Madin Darby canine kidney cell line model that, although manipulation of the ZEB/miR-200 balance is able to repeatedly switch cells between epithelial and mesenchymal states, the induction and maintenance of a stable mesenchymal phenotype requires the establishment of autocrine transforming growth factor-β (TGF-β) signaling to drive sustained ZEB expression. Furthermore, we show that prolonged autocrine TGF-β signaling induced reversible DNA methylation of the miR-200 loci with corresponding changes in miR …
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