Stable overexpression of the epithelial sodium channel alpha subunit reduces migration and proliferation in breast cancer cells.

PURPOSE: Breast cancer is the most common cancer diagnosed in women worldwide. Ion channels have emerged as novel regulators of cancer cell functions, including proliferation and migration. The epithelial sodium channel (ENaC) has a key role in blood pressure regulation, and ENaC levels affect the characteristics of several types of cancer. In breast cancer, a role for αENaC has not been investigated in migration previously nor the effect of stable overexpression of αENaC on proliferation. METHODS: Correlations of the mRNA levels for the four ENaC subunits and breast cancer survival outcomes were assessed in publicly available data and the association between αENaC and migration-related genes. Three isogenic monoclonal derivatives of MDA-MB-231 breast cancer cell lines were created with stable αENaC overexpression. Migration assays (scratch wound assay and Boyden chamber assays) and a proliferation assay (EdU) were used to determine the effect of αENaC overexpression compared to control MDA-MB-231 cells. RESULTS: Higher α- or δENaC expression was correlated with improved patient survival. Higher αENaC expression correlated with lower expression of migration-associated genes. Stable overexpression of αENaC in MDA-MB-231 cells resulted in reduced in vitro migration and proliferation of all three clones compared to parental control cells. CONCLUSION: Higher αENaC expression correlates with improved patient outcomes, and overexpression in breast cancer cells reduces both cell migration and proliferation. These results highlight the possibility of ENaC as a target for future breast cancer treatments.