Journal article

An autocrine TGF-beta/ZEB/miR-200 signaling network regulates establishment and maintenance of epithelial-mesenchymal transition

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

Molecular Biology of the Cell | AMER SOC CELL BIOLOGY | Published : 2011

Abstract

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..

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Grants

Awarded by National Breast Cancer Foundation


Funding Acknowledgements

We thank Narrelle Mancini for excellent technical assistance and members of the Goodall and Khew-Goodall labs for helpful discussions. This work was supported by fellowships from the National Breast Cancer Foundation Australia (to P.A.G. and C.P.B.) and by grants from the National Health and Medical Research Council (to G.J.G and Y.K-G) and the Cancer Council South Australia (to G.J.G., Y.K.-G., and P.A.D.). The Breast Biomarker Project, which contributed breast cancer samples, was supported by The Victorian Cancer Agency.