The Voltage-Gated Sodium Channel Beta4 Subunit Maintains Epithelial Phenotype in Mammary Cells
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The Voltage-Gated Sodium Channel Beta4 Subunit Maintains Epithelial Phenotype in Mammary Cells. / Doray, Adélaïde; Lemoine, Roxane; Severin, Marc; Chadet, Stéphanie; Lopez-Charcas, Osbaldo; Héraud, Audrey; Baron, Christophe; Besson, Pierre; Monteil, Arnaud; Pedersen, Stine Falsig; Roger, Sébastien.
In: Cells, Vol. 10, No. 7, 1624, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - The Voltage-Gated Sodium Channel Beta4 Subunit Maintains Epithelial Phenotype in Mammary Cells
AU - Doray, Adélaïde
AU - Lemoine, Roxane
AU - Severin, Marc
AU - Chadet, Stéphanie
AU - Lopez-Charcas, Osbaldo
AU - Héraud, Audrey
AU - Baron, Christophe
AU - Besson, Pierre
AU - Monteil, Arnaud
AU - Pedersen, Stine Falsig
AU - Roger, Sébastien
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - epithelial phenotype
KW - epithelial-to-mesenchymal transition
KW - mammary cells
KW - NaVβ4
KW - β-catenin
U2 - 10.3390/cells10071624
DO - 10.3390/cells10071624
M3 - Journal article
C2 - 34209614
AN - SCOPUS:85110343856
VL - 10
JO - Cells
JF - Cells
SN - 2073-4409
IS - 7
M1 - 1624
ER -
ID: 275880689