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Type: Journal article
Title: The mir-200 family and mir-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1
Author: Gregory, P.
Bert, A.
Paterson, E.
Barry, S.
Tsykin, A.
Farshid, G.
Vadas, M.
Khew-Goodall, Y.
Goodall, G.
Citation: Nature Cell Biology, 2008; 10(5):593-601
Publisher: Nature Publishing Group
Issue Date: 2008
ISSN: 1465-7392
Statement of
Philip A. Gregory, Andrew G. Bert, Emily L. Paterson, Simon C. Barry, Anna Tsykin, Gelareh Farshid, Mathew A. Vadas, Yeesim Khew-Goodall and Gregory J. Goodall
Abstract: Epithelial to mesenchymal transition (EMT) facilitates tissue remodelling during embryonic development and is viewed as an essential early step in tumour metastasis. We found that all five members of the microRNA-200 family (miR-200a, miR-200b, miR-200c, miR-141 and miR-429) and miR-205 were markedly downregulated in cells that had undergone EMT in response to transforming growth factor (TGF)- or to ectopic expression of the protein tyrosine phosphatase Pez. Enforced expression of the miR-200 family alone was sufficient to prevent TGF--induced EMT. Together, these microRNAs cooperatively regulate expression of the E-cadherin transcriptional repressors ZEB1 (also known as EF1) and SIP1 (also known as ZEB2), factors previously implicated in EMT and tumour metastasis. Inhibition of the microRNAs was sufficient to induce EMT in a process requiring upregulation of ZEB1 and/or SIP1. Conversely, ectopic expression of these microRNAs in mesenchymal cells initiated mesenchymal to epithelial transition (MET). Consistent with their role in regulating EMT, expression of these microRNAs was found to be lost in invasive breast cancer cell lines with mesenchymal phenotype. Expression of the miR-200 family was also lost in regions of metaplastic breast cancer specimens lacking E-cadherin. These data suggest that downregulation of the microRNAs may be an important step in tumour progression.
Keywords: Epithelium; Cell Line; Mesoderm; Animals; Dogs; Humans; Breast Neoplasms; Neoplasm Invasiveness; Actins; RNA-Binding Proteins; Homeodomain Proteins; Cadherins; Membrane Proteins; Nerve Tissue Proteins; Phosphoproteins; Transcription Factors; MicroRNAs; RNA, Small Interfering; Microarray Analysis; Phenotype; Genes, Reporter; Female; Transforming Growth Factor beta1; Zonula Occludens-1 Protein; Zinc Finger E-box-Binding Homeobox 1
Description: © 2008 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.
RMID: 0020080630
DOI: 10.1038/ncb1722
Appears in Collections:Paediatrics publications

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