ArticleCancer research2010
Inhibition of the Sodium-Potassium-Chloride Cotransporter Isoform-1 reduces glioma invasion.
Article in Cancer research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
78 citing papers in PubMed, 131 citations in OpenAlex.
- NKCC1: A key regulator of glioblastoma progression.Molecular oncology · 2026Article
- Targeting Ion Channels for Cancer Therapy: From Pathophysiological Mechanisms to Clinical Translation.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Super-resolution sodium MRI of human gliomas at 3T using physics-based generative artificial intelligence.Journal of neuro-oncology · 2025Article
- In Vivo and In Vitro Experimental Study Comparing the Effect of a Combination of Sodium Dichloroacetate and Valproic Acid with That of Temozolomide on Adult Glioblastoma.International journal of molecular sciences · 2025Article
- Differential Impact of Valproic Acid onBiomedicines · 2024Article
- Elastocapillary effects determine early matrix deformation by glioblastoma cell spheroids.APL bioengineering · 2024Article
- Antihypertensive drug targets and breast cancer risk: a two-sample Mendelian randomization study.European journal of epidemiology · 2024Article
- Comprehensive analyses of solute carrier family members identify SLC12A2 as a novel therapy target for colorectal cancer.Scientific reports · 2024Article
- Hypoxia, Ion Channels and Glioblastoma Malignancy.Biomolecules · 2023Review
- SPAK-dependent cotransporter activity mediates capillary adhesion and pressure during glioblastoma migration in confined spaces.Molecular biology of the cell · 2023Article
- Impact of Solute Carrier Transporters in Glioma Pathology: A Comprehensive Review.International journal of molecular sciences · 2023Review
- AQP4-independent TRPV4 modulation of plasma membrane water permeability.Frontiers in cellular neuroscience · 2023Article
- The Comparative Experimental Study of Sodium and Magnesium Dichloroacetate Effects on Pediatric PBT24 and SF8628 Cell Glioblastoma Tumors Using a Chicken Embryo Chorioallantoic Membrane Model and on Cells In Vitro.International journal of molecular sciences · 2022Article
- Different Effects of Valproic Acid onBiomedicines · 2022Article
- The Different Temozolomide Effects on Tumorigenesis Mechanisms of Pediatric Glioblastoma PBT24 and SF8628 Cell Tumor in CAM Model and on Cells In Vitro.International journal of molecular sciences · 2022Article
- Converging Mechanisms of Epileptogenesis and Their Insight in Glioblastoma.Frontiers in molecular neuroscience · 2022Review
- Ion Channels, Transporters, and Sensors Interact with the Acidic Tumor Microenvironment to Modify Cancer Progression.Reviews of physiology, biochemistry and pharmacology · 2022Review
- Targeting Ion Channels for Cancer Treatment: Current Progress and Future Challenges.Reviews of physiology, biochemistry and pharmacology · 2022Review
- Organoid Models of Glioblastoma and Their Role in Drug Discovery.Frontiers in cellular neuroscience · 2021Review
- Alterations of Ion Homeostasis in Cancer Metastasis: Implications for Treatment.Frontiers in oncology · 2021Review
18 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
Malignant gliomas metastasize throughout the brain by infiltrative cell migration into peritumoral areas. Invading cells undergo profound changes in cell shape and volume as they navigate extracellular spaces along blood vessels and white matter tracts. Volume changes are aided by the concerted release of osmotically active ions, most notably K(+) and Cl(-). Their efflux through ion channels along with obligated water causes rapid cell shrinkage. Suitable ionic gradients must be established and maintained through the activity of ion transport systems. Here, we show that the Sodium-Potassium-Chloride Cotransporter Isoform-1 (NKCC1) provides the major pathway for Cl(-) accumulation in glioma cells. NKCC1 localizes to the leading edge of invading processes, and pharmacologic inhibition using the loop diuretic bumetanide inhibits in vitro Transwell migration by 25% to 50%. Short hairpin RNA knockdowns of NKCC1 yielded a similar inhibition and a loss of bumetanide-sensitive cell volume regulation. A loss of NKCC1 function did not affect cell motility in two-dimensional assays lacking spatial constraints but manifested only when cells had to undergo volume changes during migration. Intracranial implantation of human gliomas into severe combined immunodeficient mice showed a marked reduction in cell invasion when NKCC1 function was disrupted genetically or by twice daily injection of the Food and Drug Administration-approved NKCC1 inhibitor Bumex. These data support the consideration of Bumex as adjuvant therapy for patients with high-grade gliomas.
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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.