ArticleAmerican journal of physiology. Cell physiology2011
With-No-Lysine Kinase 3 (WNK3) stimulates glioma invasion by regulating cell volume.
Article in American journal of physiology. Cell physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Systematic review of protein biomarkers of invasive behavior in glioblastoma.Molecular neurobiology · 2014Pooled it
- No lysine? No problem: the surprising roles of WNK kinases in physiology and disease.The Biochemical journal · 2026Review
- Connexin 43 drives glioblastoma cancer stem cell phenotypes through a WNK lysine-deficient protein kinase 1-c-MYC signaling axis.Cell reports · 2025Article
- Article
- CRISPR-mediated WNK4 point mutation aggravates tumor progression and weakens chemotherapy sensitivity in gastric cancer.Histology and histopathology · 2025Article
- Differential Impact of Valproic Acid onBiomedicines · 2024Article
- The Role of Ion-Transporting Proteins in Human Disease.International journal of molecular sciences · 2024Article
- Hypoxia, Ion Channels and Glioblastoma Malignancy.Biomolecules · 2023Review
- Physiological roles of chloride ions in bodily and cellular functions.The journal of physiological sciences : JPS · 2023Review
- An update regarding the role of WNK kinases in cancer.Cell death & disease · 2022Review
- 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
- Ion Channels, Transporters, and Sensors Interact with the Acidic Tumor Microenvironment to Modify Cancer Progression.Reviews of physiology, biochemistry and pharmacology · 2022Review
- Silencing of the lncRNA H19 enhances sensitivity to X-ray and carbon-ions through the miR-130a-3p /WNK3 signaling axis in NSCLC cells.Cancer cell international · 2021Article
- Phosphorylated WNK kinase networks in recoded bacteria recapitulate physiological function.Cell reports · 2021Article
- WNK3 promotes the invasiveness of glioma cell lines under hypoxia by inducing the epithelial-to-mesenchymal transition.Translational neuroscience · 2021Article
- NKCC1 involvement in the epithelial-to-mesenchymal transition is a prognostic biomarker in gliomas.PeerJ · 2020Article
- Role of NKCC1 Activity in Glioma KFrontiers in physiology · 2020Article
- Control of Podocyte and Glomerular Capillary Wall Structure and Elasticity by WNK1 Kinase.Frontiers in cell and developmental biology · 2020Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Among the most prevalent and deadly primary brain tumors, high-grade gliomas evade complete surgical resection by diffuse invasion into surrounding brain parenchyma. Navigating through tight extracellular spaces requires invading glioma cells to alter their shape and volume. Cell volume changes are achieved through transmembrane transport of osmolytes along with obligated water. The sodium-potassium-chloride cotransporter isoform-1 (NKCC1) plays a pivotal role in this process, and previous work has demonstrated that NKCC1 inhibition compromises glioma invasion in vitro and in vivo by interfering with the required cell volume changes. In this study, we show that NKCC1 activity in gliomas requires the With-No-Lysine Kinase-3 (WNK3) kinase. Western blots of patient biopsies and patient-derived cell lines shows prominent expression of Ste-20-related, proline-alanine-rich kinase (SPAK), oxidative stress response kinase (OSR1), and WNK family members 1, 3, and 4. Of these, only WNK3 colocalized and coimmunoprecipitated with NKCC1 upon changes in cell volume. Stable knockdown of WNK3 using specific short hairpin RNA constructs completely abolished NKCC1 activity, as measured by the loss of bumetanide-sensitive cell volume regulation. Consequently, WNK3 knockdown cells showed a reduced ability to invade across Transwell barriers and lacked bumetanide-sensitive migration. This data indicates that WNK3 is an essential regulator of NKCC1 and that WNK3 activates NKCC1-mediated ion transport necessary for cell volume changes associated with cell invasion.
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Registered trials
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