A reciprocal repression between ZEB1 and members of the miR‐200 family promotes EMT and invasion in cancer cells

EMBO Reports - Tập 9 Số 6 - Trang 582-589 - 2008
Ulrike Burk1, Jörg Schubert1,2,3, Ulrich F. Wellner1, Otto Schmalhofer1, Elizabeth Vincan4,5, Simone Spaderna1, Thomas Brabletz1
1Department of Visceral Surgery, University of Freiburg Hugstetter Strasse 55 79106 Freiburg Germany
2Department of Visceral Surgery, and
3Faculty of Biology, University of Freiburg Hugstetter Strasse 55 79106 Freiburg Germany
4Department of Anatomy and Cell Biology, University of Melbourne, Cnr Grattan Street, Parkville, Victoria 3010, Australia
5Department of Anatomy and Cell Biology, University of Melbourne, Parkville, Victoria, Australia

Tóm tắt

The embryonic programme ‘epithelial–mesenchymal transition’ (EMT) is thought to promote malignant tumour progression. The transcriptional repressor zinc‐finger E‐box binding homeobox 1 (ZEB1) is a crucial inducer of EMT in various human tumours, and was recently shown to promote invasion and metastasis of tumour cells. Here, we report that ZEB1 directly suppresses transcription of microRNA‐200 family members miR‐141 and miR‐200c, which strongly activate epithelial differentiation in pancreatic, colorectal and breast cancer cells. Notably, the EMT activators transforming growth factor β2 and ZEB1 are the predominant targets downregulated by these microRNAs. These results indicate that ZEB1 triggers an microRNA‐mediated feedforward loop that stabilizes EMT and promotes invasion of cancer cells. Alternatively, depending on the environmental trigger, this loop might switch and induce epithelial differentiation, and thus explain the strong intratumorous heterogeneity observed in many human cancers.

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EMBO Reports

Tập 9 Số 6

582-589

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