Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 May;187(1):31-43.
doi: 10.1007/s10549-021-06133-7. Epub 2021 Feb 25.

The epithelial sodium channel has a role in breast cancer cell proliferation

Adam W Ware  1 , Joshua J Harris  2 , Tania L Slatter  2 , Heather E Cunliffe  2 , Fiona J McDonald  3
Affiliations

The epithelial sodium channel has a role in breast cancer cell proliferation

Adam W Ware et al. Breast Cancer Res Treat. 2021 May.

Abstract

Purpose: Breast cancer is the most common cancer affecting women worldwide with half a million associated deaths annually. Despite a huge global effort, the pathways of breast cancer progression are not fully elucidated. Ion channels have recently emerged as novel regulators of cancer cell proliferation and metastasis. The epithelial sodium channel, ENaC, made up of α, β and γ subunits is well known for its role in Na+ reabsorption in epithelia, but a number of novel roles for ENaC have been described, including potential roles in cancer. A role for ENaC in breast cancer, however, has yet to be described. Therefore, the effects of ENaC level and activity on breast cancer proliferation were investigated.

Methods: Through the publicly available SCAN-B dataset associations between αENaC mRNA expression and breast cancer subtypes, proliferation markers and epithelial-mesenchymal transition markers (EMT) were assessed. αENaC expression, through overexpression or siRNA-mediated knockdown, and activity, through the ENaC-specific inhibitor amiloride, were altered in MCF7, T47D, BT549, and MDAMB231 breast cancer cells. MTT and EdU cell proliferation assays were used to determine the effect of these manipulations on breast cancer cell proliferation.

Results: High αENaC mRNA expression was associated with less aggressive and less proliferative breast cancer subtypes and with reduced expression of proliferation markers. Decreased αENaC expression or activity, in the mesenchymal breast cancer cell lines BT549 and MDAMB231, increased breast cancer cell proliferation. Conversely, increased αENaC expression decreased breast cancer cell proliferation.

Conclusion: αENaC expression is associated with a poor prognosis in breast cancer and is a novel regulator of breast cancer cell proliferation. Taken together, these results identify ENaC as a potential future therapeutic target.

Keywords: Breast cancer; Epithelial sodium channel (ENaC); Epithelial–mesenchymal transition (EMT); Proliferation.

PubMed Disclaimer

References

    1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M et al (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136(5):E359–E386 - PubMed - PMC
    1. Ghoncheh M, Pournamdar Z, Salehiniya H (2016) Incidence and mortality and epidemiology of breast cancer in the world. Asian Pac J Cancer Prev 17(S3):43–46 - PubMed
    1. Gupta GP, Massague J (2006) Cancer metastasis: building a framework. Cell 127(4):679–695 - PubMed
    1. Seyfried TN, Huysentruyt LC (2013) On the origin of cancer metastasis. Crit Rev Oncog 18(1–2):43–73 - PubMed - PMC
    1. Cummings MC, Simpson PT, Reid LE, Jayanthan J, Skerman J, Song S et al (2014) Metastatic progression of breast cancer: insights from 50 years of autopsies. J Pathol 232(1):23–31 - PubMed

LinkOut - more resources