ArticlePflugers Archiv : European journal of physiology2015
Suppression of PPARβ, and DHA treatment, inhibit NaV1.5 and NHE-1 pro-invasive activities.
Article in Pflugers Archiv : European journal of physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 28 citations in OpenAlex.
- Effects of NaCell biochemistry and biophysics · 2025Review
- Voltage-gated sodium channels: from roles and mechanisms in the metastatic cell behavior to clinical potential as therapeutic targets.Frontiers in pharmacology · 2023Review
- Spider venom-derived peptide JZTX-14 prevents migration and invasion of breast cancer cellsFrontiers in pharmacology · 2023Article
- Dynamic synovial fibroblasts are modulated by NBCn1 as a potential target in rheumatoid arthritis.Experimental & molecular medicine · 2022Article
- Targeting Ion Channels for Cancer Treatment: Current Progress and Future Challenges.Reviews of physiology, biochemistry and pharmacology · 2022Review
- Pharmacological and nutritional targeting of voltage-gated sodium channels in the treatment of cancers.iScience · 2021Review
- Towards an Integral Therapeutic Protocol for Breast Cancer Based upon the New HInternational journal of molecular sciences · 2020Review
- Roles of endogenous ether lipids and associated PUFAs in the regulation of ion channels and their relevance for disease.Journal of lipid research · 2020Review
- A New and Integral Approach to the Etiopathogenesis and Treatment of Breast Cancer Based upon Its Hydrogen Ion Dynamics.International journal of molecular sciences · 2020Review
- The Functional Role of Voltage-Gated Sodium Channel Nav1.5 in Metastatic Breast Cancer.Frontiers in pharmacology · 2020Review
- Actions and Mechanisms of Polyunsaturated Fatty Acids on Voltage-Gated Ion Channels.Frontiers in physiology · 2017Review
- SCN4B acts as a metastasis-suppressor gene preventing hyperactivation of cell migration in breast cancer.Nature communications · 2016Article
- Voltage-gated sodium channels and cancer: is excitability their primary role?Frontiers in pharmacology · 2015Review
- Therapeutic Value of Voltage-Gated Sodium Channel Inhibitors in Breast, Colorectal, and Prostate Cancer: A Systematic Review.Frontiers in pharmacology · 2015Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Peroxisome proliferator-activated receptor β (PPARβ) and NaV1.5 voltage-gated sodium channels have independently been shown to regulate human breast cancer cell invasiveness. The n-3 polyunsaturated docosahexaenoic acid (DHA, 22:6n-3), a natural ligand of PPAR, is effective in increasing survival and chemotherapy efficacy in breast cancer patient with metastasis. DHA reduces breast cancer cell invasiveness and it also inhibits PPARβ expression. We have shown previously that NaV1.5 promotes MDA-MB-231 breast cancer cells invasiveness by potentiating the activity of Na(+)/H(+) exchanger type 1 (NHE-1), the major regulator of H(+) efflux in these cells. We report here that DHA inhibited NaV1.5 current and NHE-1 activity in human breast cancer cells, and in turn reduced NaV1.5-dependent cancer cell invasiveness. For the first time, we show that antagonizing PPARβ, or inhibiting its expression, reduced NaV1.5 mRNA and protein expression and NaV1.5 current, as well as NHE-1 activity and cell invasiveness. Consistent with these results, the DHA-induced reduction of both NaV1.5 expression and NHE-1 activity was abolished in cancer cells knocked-down for the expression of PPARβ (shPPARβ). This demonstrates a direct link between the inhibition of PPARβ expression and the inhibition of Nav1.5/NHE-1 activities and breast cancer cell invasiveness. This study provides new mechanistic data advocating for the use of natural fatty acids such as DHA to block the development of breast cancer metastases.
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