The epithelial sodium channel has a role in breast cancer cell proliferation
Autor: | Tania L. Slatter, Heather E. Cunliffe, Joshua J. Harris, Adam W. Ware, Fiona J. McDonald |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Epithelial sodium channel Cancer Research Gene knockdown business.industry Cell growth Mesenchymal stem cell Cancer medicine.disease Amiloride Metastasis 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Breast cancer Oncology 030220 oncology & carcinogenesis medicine Cancer research skin and connective tissue diseases business medicine.drug |
Zdroj: | Breast Cancer Research and Treatment. 187:31-43 |
ISSN: | 1573-7217 0167-6806 |
Popis: | 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. 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. 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. 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. |
Databáze: | OpenAIRE |
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