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Updated: Jun 12, 2025
Author Spotlight: Exploring the Role of Ion Channels in Cancer: Characterization and Potential Treatment Approaches
Published on: June 16, 2023
Targeting Ca2+-activated K+ channels in glioma
Yuequ Zhang1, Hennrique Taborda Ribas2, Sheila M B Winnischofer3
1Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy (GRIP), Faculty of Science and Engineering, University of Groningen, Groningen, the Netherlands.
Abstract:
Glioma affects millions of people worldwide and there is a lack of effective therapies. Glioblastoma multiforme (GBM) is the most common and deadliest form of primary brain tumor in adults. Emerging evidence indicated that targeting ion channels may be a promising therapeutic approach for GBM. Altered expression and activity of the Ca2+- activated K+ (KCa) channels have been reported in GBM patients. Generally, large-conductance KCa (BKCa) channels and intermediate-conductance KCa (IKCa or SK4) channels are highly expressed in glioma samples compared to healthy control brain tissue. Analyzing TCGA database, the expression of KCNMB1 (encoding the BKCa channel protein) and KCNN4 (encoding the KCa3.1/IKCa protein) genes was upregulated, while KCNN1 (encoding the KCa2.1 protein) gene expression was downregulated in GBM patients grade IV compared to GBM patients grade I or II. The gene expression and activity of KCa channels may contribute to survival outcomes, by regulating cellular processes like cell proliferation and migration. Importantly, modulation of the activity of KCa channels reduced the proliferation and migration of GBM cells and suppressed glioma progression both in vivo and in vitro cell models for GBM. Herein, we aim to review how modulation of the activity of KCa channels impacts tumor development in terms of proliferation, cell death, invasion, metabolism and immune system in GBM.
Insights
Targeting calcium-activated potassium (KCa) channels shows promise for glioblastoma multiforme (GBM) therapy. Modulating these channels inhibits GBM cell proliferation and migration, offering a potential new treatment strategy.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Channelopathies
Background:
- Glioblastoma multiforme (GBM) is an aggressive brain tumor with limited effective treatments.
- Ion channels, particularly Ca2+-activated K+ (KCa) channels, are increasingly recognized as potential therapeutic targets in GBM.
- Aberrant expression and activity of KCa channels, including BKCa and IKCa/SK4, are observed in glioma.
Purpose of the Study:
- To review the impact of modulating KCa channel activity on GBM development.
- To explore how KCa channel modulation affects key tumor processes such as proliferation, cell death, invasion, metabolism, and immune response.
Main Methods:
- Analysis of The Cancer Genome Atlas (TCGA) database for KCa channel gene expression (KCNMB1, KCNN4, KCNN1) in different GBM grades.
- Review of in vitro and in vivo studies demonstrating the effects of KCa channel modulation on GBM cell behavior.
- Examination of cellular processes influenced by KCa channels in GBM.
Main Results:
- Upregulation of KCNMB1 (BKCa) and KCNN4 (KCa3.1/IKCa) gene expression, and downregulation of KCNN1 (KCa2.1) in high-grade GBM.
- KCa channel activity is linked to GBM cell proliferation and migration.
- Inhibition of KCa channels suppressed GBM cell proliferation and migration in preclinical models.
Conclusions:
- KCa channels play a significant role in GBM progression.
- Modulation of KCa channel activity presents a promising therapeutic strategy for GBM.
- Further research into KCa channel function in GBM could lead to novel treatment approaches.
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