Snail controls differentiation of hepatocytes by repressing HNF4α expression

Carla Cicchini, Daniela Filippini, Sabrina Coen, Alessandra Marchetti, Claudio Cavallari, Ilaria Laudadio, Francesca M. Spagnoli, Tonino Alonzi, Marco Tripodi

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)230-238
Number of pages9
JournalJournal of Cellular Physiology
Volume209
Issue number1
DOIs
Publication statusPublished - Oct 2006

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

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