A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells
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 a...
| Main Authors: | , , , , , , |
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| Format: | Journal Article |
| Published: |
2008
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| Online Access: | http://hdl.handle.net/20.500.11937/42318 |
| _version_ | 1848756387052519424 |
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| author | Burk, U. Schubert, J. Wellner, U. Schmalhofer, O. Vincan, Elizabeth Spaderna, S. Brabletz, T. |
| author_facet | Burk, U. Schubert, J. Wellner, U. Schmalhofer, O. Vincan, Elizabeth Spaderna, S. Brabletz, T. |
| author_sort | Burk, U. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | 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 ß2 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. |
| first_indexed | 2025-11-14T09:11:23Z |
| format | Journal Article |
| id | curtin-20.500.11937-42318 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T09:11:23Z |
| publishDate | 2008 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-423182023-02-22T06:24:18Z A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells Burk, U. Schubert, J. Wellner, U. Schmalhofer, O. Vincan, Elizabeth Spaderna, S. Brabletz, T. 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 ß2 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. 2008 Journal Article http://hdl.handle.net/20.500.11937/42318 10.1038/embor.2008.74 unknown |
| spellingShingle | Burk, U. Schubert, J. Wellner, U. Schmalhofer, O. Vincan, Elizabeth Spaderna, S. Brabletz, T. A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells |
| title | A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells |
| title_full | A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells |
| title_fullStr | A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells |
| title_full_unstemmed | A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells |
| title_short | A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells |
| title_sort | reciprocal repression between zeb1 and members of the mir-200 family promotes emt and invasion in cancer cells |
| url | http://hdl.handle.net/20.500.11937/42318 |