Résumé
The SCN4B gene, encoding for the NaVβ4 subunit of voltage-gated sodium channels, was recently found to be expressed in normal epithelial cells and down-regulated in several cancers. However, its function in normal epithelial cells is not characterized. In this study, we demonstrate that reducing NaVβ4 expression in MCF10A non-cancer mammary epithelial cells generates important morphological changes observed both in two-dimensional cultures and in three-dimensional cysts. Most notably the loss of NaVβ4 induces a complete loss of epithelial organisation in cysts and increases proteolytic activity towards the extracellular matrix. Loss of epithelial morphology was associated with an increased degradation of β-catenin, reduced E-cadherin expression and induction of mesenchymal markers N-cadherin, vimentin, α-SMA expression. Overall, our results suggest that Navβ4 may participate in the maintenance of the epithelial phenotype in mammary cells and that its down regulation might be a determining step in early carcinogenesis.