ArticlePLoS biology2012
Regulation of brain tumor dispersal by NKCC1 through a novel role in focal adhesion regulation.
Article in PLoS biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers, 1 of them a synthesis that pooled it.
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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
104 citing papers in PubMed, 1 synthesis or guideline pooled it, 148 citations in OpenAlex.
- Systematic review of protein biomarkers of invasive behavior in glioblastoma.Molecular neurobiology · 2014Pooled it
- NKCC1: A key regulator of glioblastoma progression.Molecular oncology · 2026Article
- Review
- Synthesis of new sulfoximines and sulfonimidamides derivatives as NKCC1 inhibitors.Frontiers in chemistry · 2026Article
- The Role of mTOR Signaling in Tumor-Induced Alterations to Neuronal Function in Diffusely Infiltrating Glioma.Biomedicines · 2025Review
- Connexin 43 drives glioblastoma cancer stem cell phenotypes through a WNK lysine-deficient protein kinase 1-c-MYC signaling axis.Cell reports · 2025Article
- Comparison of the Effect of the Combination of Sodium Valproate and Sodium Dichloroacetate on the Expression ofPharmaceutics · 2025Article
- Differential Impact of Valproic Acid onBiomedicines · 2024Article
- Elastocapillary effects determine early matrix deformation by glioblastoma cell spheroids.APL bioengineering · 2024Article
- Comprehensive analyses of solute carrier family members identify SLC12A2 as a novel therapy target for colorectal cancer.Scientific reports · 2024Article
- Intrinsic and Microenvironmental Drivers of Glioblastoma Invasion.International journal of molecular sciences · 2024Review
- The Role of Ion-Transporting Proteins in Human Disease.International journal of molecular sciences · 2024Article
- T cell migration requires ion and water influx to regulate actin polymerization.Nature communications · 2023Article
- Physiological roles of chloride ions in bodily and cellular functions.The journal of physiological sciences : JPS · 2023Review
- SPAK-dependent cotransporter activity mediates capillary adhesion and pressure during glioblastoma migration in confined spaces.Molecular biology of the cell · 2023Article
- Perivascular invasion of primary human glioblastoma cells in organotypic human brain slices: human cells migrating in human brain.Journal of neuro-oncology · 2023Article
- Impact of Solute Carrier Transporters in Glioma Pathology: A Comprehensive Review.International journal of molecular sciences · 2023Review
- Expression patterns of NKCC1 in neurons and non-neuronal cells during cortico-hippocampal development.Cerebral cortex (New York, N.Y. : 1991) · 2023Article
- Ion Channels in Gliomas-From Molecular Basis to Treatment.International journal of molecular sciences · 2023Review
- Nucleic acid drug vectors for diagnosis and treatment of brain diseases.Signal transduction and targeted therapy · 2023Review
44 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
12 authors at 4 institutions in 1 country.
Funding
Abstract
Glioblastoma (GB) is a highly invasive and lethal brain tumor due to its universal recurrence. Although it has been suggested that the electroneutral Na(+)-K(+)-Cl(-) cotransporter 1 (NKCC1) can play a role in glioma cell migration, the precise mechanism by which this ion transporter contributes to GB aggressiveness remains poorly understood. Here, we focused on the role of NKCC1 in the invasion of human primary glioma cells in vitro and in vivo. NKCC1 expression levels were significantly higher in GB and anaplastic astrocytoma tissues than in grade II glioma and normal cortex. Pharmacological inhibition and shRNA-mediated knockdown of NKCC1 expression led to decreased cell migration and invasion in vitro and in vivo. Surprisingly, knockdown of NKCC1 in glioma cells resulted in the formation of significantly larger focal adhesions and cell traction forces that were approximately 40% lower than control cells. Epidermal growth factor (EGF), which promotes migration of glioma cells, increased the phosphorylation of NKCC1 through a PI3K-dependant mechanism. This finding is potentially related to WNK kinases. Taken together, our findings suggest that NKCC1 modulates migration of glioma cells by two distinct mechanisms: (1) through the regulation of focal adhesion dynamics and cell contractility and (2) through regulation of cell volume through ion transport. Due to the ubiquitous expression of NKCC1 in mammalian tissues, its regulation by WNK kinases may serve as new therapeutic targets for GB aggressiveness and can be exploited by other highly invasive neoplasms.
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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.