ArticleThe Journal of biological chemistry2010
Molecular interaction and functional regulation of ClC-3 by Ca2+/calmodulin-dependent protein kinase II (CaMKII) in human malignant glioma.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
70 citing papers in PubMed, 120 citations in OpenAlex.
- H3 dopaminylation and CaMKII modulate diffuse midline glioma response to CDK9 inhibition.bioRxiv : the preprint server for biology · 2026Article
- Targeting Ion Channels for Cancer Therapy: From Pathophysiological Mechanisms to Clinical Translation.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Intrinsic and Microenvironmental Drivers of Glioblastoma Invasion.International journal of molecular sciences · 2024Review
- Chloride Channel-3 (ClC-3) Modifies the Trafficking of Leucine-Rich Repeat-Containing 8A (LRRC8A) Anion Channels.The Journal of membrane biology · 2023Article
- Ion Channels in Gliomas-From Molecular Basis to Treatment.International journal of molecular sciences · 2023Review
- The CaMKII/MLC1 Axis Confers CaCells · 2022Article
- Trifluoperazine and Its Analog Suppressed the Tumorigenicity of Non-Small Cell Lung Cancer Cell; Applicability of Antipsychotic Drugs to Lung Cancer Treatment.Biomedicines · 2022Article
- Ion Transport and Radioresistance.Reviews of physiology, biochemistry and pharmacology · 2022Review
- Calcium/calmodulin-dependent protein kinase II associates with the KFrontiers in neuroanatomy · 2022Article
- Bioelectric Dysregulation in Cancer Initiation, Promotion, and Progression.Frontiers in oncology · 2022Review
- ClC-c regulates the proliferation of intestinal stem cells via the EGFR signalling pathway in Drosophila.Cell proliferation · 2022Article
- Electrotherapies for Glioblastoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Review
- CaCancers · 2021Review
- Ion Channels in Glioma Malignancy.Reviews of physiology, biochemistry and pharmacology · 2021Review
- Integrated Proteogenomic Characterization across Major Histological Types of Pediatric Brain Cancer.Cell · 2020Article
- Ion Channels and Their Role in the Pathophysiology of Gliomas.Molecular cancer therapeutics · 2020Review
- Elemental characterization of oral cavity squamous cell carcinoma and its relationship with smoking, prognosis and survival.Scientific reports · 2020Article
- Article
- The Role of Calmodulin in Tumor Cell Migration, Invasiveness, and Metastasis.International journal of molecular sciences · 2020Review
- Up-regulation of CLIC1 activates MYC signaling and forms a positive feedback regulatory loop with MYC in Hepatocellular carcinoma.American journal of cancer research · 2020Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Glioblastoma multiforme is the most common and lethal primary brain cancer in adults. Tumor cells diffusely infiltrate the brain making focal surgical and radiation treatment challenging. The invasion of glioma cells into normal brain is facilitated by the activity of ion channels aiding dynamic regulation of cell volume. Recent studies have specifically implicated ClC-3, a voltage-gated chloride channel, in this process. However, the interaction between ClC-3 activity and cell movement is poorly understood. Here, we demonstrate that ClC-3 is highly expressed on the plasma membrane of human glioma cells where its activity is regulated through phosphorylation via Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). Intracellular infusion of autoactivated CaMKII via patch pipette enhanced chloride currents 3-fold, and this regulation was inhibited by autocamtide-2 related inhibitory peptide, a CaMKII-specific inhibitor. CaMKII modulation of chloride currents was also lost upon stable small hairpin RNA knockdown of ClC-3 channels indicating a specific interaction of ClC-3 and CaMKII. In ClC-3-expressing cells, inhibition of CaMKII reduced glioma invasion to the same extent as direct inhibition of ClC-3. The importance of the molecular interaction of ClC-3 and CaMKII is further supported by our finding that CaMKII co-localizes and co-immunoprecipitates with ClC-3. ClC-3 and CaMKII also co-immunoprecipitate in tissue biopsies from patients diagnosed with grade IV glioblastoma. These tumor samples show 10-fold higher ClC-3 protein expression than nonmalignant brain. These data suggest that CaMKII is a molecular link translating intracellular calcium changes, which are intrinsically associated with glioma migration, to changes in ClC-3 conductance required for cell movement.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.