McQueen Sarah R A, Chin Wey Qi, Cunliffe Heather E, McDonald Fiona J
Department of Physiology, School of Biomedical Sciences, University of Otago, PO Box 56, Dunedin, 9054, New Zealand.
Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
Breast Cancer Res Treat. 2025 Jun;211(3):595-604. doi: 10.1007/s10549-025-07667-w. Epub 2025 Apr 12.
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.
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.
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.
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.
乳腺癌是全球女性中最常被诊断出的癌症。离子通道已成为癌细胞功能（包括增殖和迁移）的新型调节因子。上皮钠通道（ENaC）在血压调节中起关键作用，并且ENaC水平会影响几种癌症类型的特征。在乳腺癌中，αENaC在迁移方面的作用以及αENaC稳定过表达对增殖的影响此前尚未得到研究。
在公开数据中评估了四种ENaC亚基的mRNA水平与乳腺癌生存结果的相关性，以及αENaC与迁移相关基因之间的关联。创建了MDA-MB-231乳腺癌细胞系的三种同基因单克隆衍生物，使其稳定过表达αENaC。与对照MDA-MB-231细胞相比，使用迁移试验（划痕伤口试验和博伊登室试验）和增殖试验（EdU）来确定αENaC过表达的影响。
较高的α-或δENaC表达与患者生存率提高相关。较高的αENaC表达与迁移相关基因的较低表达相关。与亲本对照细胞相比，MDA-MB-231细胞中αENaC的稳定过表达导致所有三个克隆的体外迁移和增殖减少。
较高的αENaC表达与患者预后改善相关，并且在乳腺癌细胞中的过表达会降低细胞迁移和增殖。这些结果突出了ENaC作为未来乳腺癌治疗靶点的可能性。
