Snail controls differentiation of hepatocytes by repressing HNF4α expression
Article first published online: 6 JUL 2006
Copyright © 2006 Wiley-Liss, Inc.
Journal of Cellular Physiology
Volume 209, Issue 1, pages 230–238, October 2006
How to Cite
Cicchini, C., Filippini, D., Coen, S., Marchetti, A., Cavallari, C., Laudadio, I., Spagnoli, F. M., Alonzi, T. and Tripodi, M. (2006), Snail controls differentiation of hepatocytes by repressing HNF4α expression. J. Cell. Physiol., 209: 230–238. doi: 10.1002/jcp.20730
- Issue published online: 26 JUL 2006
- Article first published online: 6 JUL 2006
- Manuscript Accepted: 7 JUN 2006
- Manuscript Received: 2 MAY 2006
- AIRC Associazione Italiana Ricerca sul Cancro
- MIUR (Ministero dell'Università e Ricerca Scientifica, Progetti di Ateneo and Cofin 2004)
- Ministero della Salute (Regione autonoma della Sardegna Ricerca Finalizzata 2003 and Ricerca Finalizzata 2004
Epithelial-to-mesenchymal transition (EMT) is a coordinated process, occurring both during morphogenesis and tumor progression, that allows epithelial cells to dissociate from initial contacts and migrate to secondary sites. The transcriptional repressors of the Snail family induce EMT in different epithelial cell lines and their expression is strictly correlated with EMT during the development and progression of carcinomas. We have previously shown that EMT in hepatocytes correlates with the downregulation of hepatic differentiation key factors HNFs (hepatocyte nuclear factors), and in particular of HNF4α. Here, we demonstrate that Snail overexpression is sufficient (i) to induce EMT in hepatocytes with conversion of morphology, downregulation of several epithelial adhesion molecules, reduction of proliferation and induction of matrix metalloproteinase 2 expression and, (ii) most relevantly, to repress the transcription of the HNF4α gene through a direct binding to its promoter. These finding demonstrate that Snail is at the crossroads of the regulation of EMT in hepatocytes by a dual control of epithelial morphogenesis and differentiation. J. Cell. Physiol. 209: 230–238, 2006. © 2006 Wiley-Liss, Inc.