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The Voltage-Gated Sodium Channel Beta4 Subunit Maintains Epithelial Phenotype in Mammary Cells.

Cells (2021-07-03)
Adélaïde Doray, Roxane Lemoine, Marc Severin, Stéphanie Chadet, Osbaldo Lopez-Charcas, Audrey Héraud, Christophe Baron, Pierre Besson, Arnaud Monteil, Stine Falsig Pedersen, Sébastien Roger
ABSTRACT

The SCN4B gene, coding 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 has not been characterized. In this study, we demonstrated that reducing NaVβ4 expression in MCF10A non-cancer mammary epithelial cells generated important morphological changes observed both in two-dimensional cultures and in three-dimensional cysts. Most notably, the loss of NaVβ4 induced a complete loss of epithelial organisation in cysts and increased 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, and α-SMA expression. Overall, our results suggest that Navβ4 may participate in the maintenance of the epithelial phenotype in mammary cells and that its downregulation might be a determining step in early carcinogenesis.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
SIGMAFAST Protease Inhibitor Cocktail Tablets, EDTA-Free, for use in purification of Histidine-tagged proteins
Sigma-Aldrich
Anti-SCN4B antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution