Snail controls differentiation of hepatocytes by repressing HNF4alpha expression
| Autor: | Sabrina Coen, Marco Tripodi, Claudio Cavallari, Daniela Filippini, Tonino Alonzi, Ilaria Laudadio, Francesca M. Spagnoli, Alessandra Marchetti, Carla Cicchini |
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| Rok vydání: | 2006 |
| Předmět: |
Physiology
Cellular differentiation Clinical Biochemistry Morphogenesis Protein Array Analysis Down-Regulation Electrophoretic Mobility Shift Assay Snail Biology Transfection Epithelium Mice Downregulation and upregulation biology.animal Animals Promoter Regions Genetic Cell Proliferation Cell adhesion molecule Cell growth Cell Differentiation Cell Biology Cell biology Hepatocyte nuclear factors Hepatocyte Nuclear Factor 4 Tumor progression embryonic structures Hepatocytes Snail Family Transcription Factors Transcription Factors |
| Zdroj: | Journal of cellular physiology. 209(1) |
| ISSN: | 0021-9541 |
| Popis: | 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 HNF4alpha. 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 HNF4alpha 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. |
| Databáze: | OpenAIRE |
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