ArticleGenes & development2012
Voltage-gated potassium channel EAG2 controls mitotic entry and tumor growth in medulloblastoma via regulating cell volume dynamics.
Article in Genes & development, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 85 citations in OpenAlex.
- Signal control during tissue regeneration in adult animals.Nature reviews. Molecular cell biology · 2026Review
- Role of repulsive guidance signaling and GPR180 in pediatric low-grade glioma infiltration.NPJ precision oncology · 2025Article
- A forward genetic screen identifies potassium channel essentiality in SHH medulloblastoma maintenance.Developmental cell · 2025Article
- Targeting Ion Channels: Blockers Suppress Calcium Signals and Induce Cytotoxicity Across Medulloblastoma Cell Models.Bioengineering (Basel, Switzerland) · 2025Article
- Exploring the Role of the KCNK1 Potassium Channel and Its Inhibition Using Quinidine in Treating Head and Neck Squamous Cell Carcinoma.Clinical and experimental otorhinolaryngology · 2024Article
- Understanding the immunosuppressive microenvironment of glioma: mechanistic insights and clinical perspectives.Journal of hematology & oncology · 2024Review
- The scale of zebrafish pectoral fin buds is determined by intercellular K+ levels and consequent Ca2+-mediated signaling via retinoic acid regulation of Rcan2 and Kcnk5b.PLoS biology · 2024Article
- Exploring the Role of Surface and Mitochondrial ATP-Sensitive Potassium Channels in Cancer: From Cellular Functions to Therapeutic Potentials.International journal of molecular sciences · 2024Review
- Pan-cancer ion transport signature reveals functional regulators of glioblastoma aggression.The EMBO journal · 2024Article
- A designer peptide against the EAG2-Kvβ2 potassium channel targets the interaction of cancer cells and neurons to treat glioblastoma.Nature cancer · 2023Article
- Neurons as stromal drivers of nervous system cancer formation and progression.Developmental cell · 2023Review
- Review
- A novel loss-of-function mutation of the voltage-gated potassium channel Kv10.2 involved in epilepsy and autism.Orphanet journal of rare diseases · 2022Article
- The role of potassium channels in the proliferation and migration of endometrial adenocarcinoma HEC1-A cells.Molecular biology reports · 2022Article
- Elevated Kir2.1/nuclear N2ICD defines a highly malignant subtype of non-WNT/SHH medulloblastomas.Signal transduction and targeted therapy · 2022Article
- Ion Channels in Cancer: Orchestrators of Electrical Signaling and Cellular Crosstalk.Reviews of physiology, biochemistry and pharmacology · 2022Review
- Tubulin Isotypes: Emerging Roles in Defining Cancer Stem Cell Niche.Frontiers in immunology · 2022Review
- Conformation-sensitive antibody reveals an altered cytosolic PAS/CNBh assembly during hERG channel gating.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Article
- Activation of AMPK sensitizes medulloblastoma to Vismodegib and overcomes Vismodegib-resistance.FASEB bioAdvances · 2021Article
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Authors and funding
20 authors at 8 institutions in 4 countries.
Funding
Abstract
Medulloblastoma (MB) is the most common pediatric CNS malignancy. We identify EAG2 as an overexpressed potassium channel in MBs across different molecular and histological subgroups. EAG2 knockdown not only impairs MB cell growth in vitro, but also reduces tumor burden in vivo and enhances survival in xenograft studies. Mechanistically, we demonstrate that EAG2 protein is confined intracellularly during interphase but is enriched in the plasma membrane during late G2 phase and mitosis. Disruption of EAG2 expression results in G2 arrest and mitotic catastrophe associated with failure of premitotic cytoplasmic condensation. While the tumor suppression function of EAG2 knockdown is independent of p53 activation, DNA damage checkpoint activation, or changes in the AKT pathway, this defective cell volume control is specifically associated with hyperactivation of the p38 MAPK pathway. Inhibition of the p38 pathway significantly rescues the growth defect and G2 arrest. Strikingly, ectopic membrane expression of EAG2 in cells at interphase results in cell volume reduction and mitotic-like morphology. Our study establishes the functional significance of EAG2 in promoting MB tumor progression via regulating cell volume dynamics, the perturbation of which activates the tumor suppressor p38 MAPK pathway, and provides clinical relevance for targeting this ion channel in human MBs.
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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.