A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells.
EMBO Rep
; 9(6): 582-9, 2008 Jun.
Article
em En
| MEDLINE
| ID: mdl-18483486
ABSTRACT
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 beta2 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Diferenciação Celular
/
Proteínas de Homeodomínio
/
MicroRNAs
/
Neoplasias
Limite:
Animals
/
Humans
Idioma:
En
Revista:
EMBO Rep
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Alemanha