ArticleCell death & disease2022
Acidosis induces RIPK1-dependent death of glioblastoma stem cells via acid-sensing ion channel 1a.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- Monocyte-hitchhiking system for the targeted delivery of paclitaxel-loaded PLGA nanoparticles to glioblastoma in mice.Journal of nanobiotechnology · 2026Article
- Unlocking glioma vulnerabilities: targeting regulated cell death pathways for innovative therapies.Cell death discovery · 2026Review
- Deciphering the Role of Functional Ion Channels in Cancer Stem Cells (CSCs) and Their Therapeutic Implications.International journal of molecular sciences · 2025Review
- PFKM-Mediated Glycolysis: A Pathway for ASIC1 to Enhance Cell Survival in the Acidic Microenvironment of Liver Cancer.Biomolecules · 2025Article
- Review
- Enhanced glycolysis causes extracellular acidification and activates acid-sensing ion channel 1a in hypoxic pulmonary hypertension.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- ASIC3-activated key enzymes of de novo lipid synthesis supports lactate-driven EMT and the metastasis of colorectal cancer cells.Cell communication and signaling : CCS · 2024Article
- Functional expression of the proton sensors ASIC1a, TMEM206, and OGR1 together with BKPflugers Archiv : European journal of physiology · 2024Article
- Acid-sensing ion channels and downstream signalling in cancer cells: is there a mechanistic link?Pflugers Archiv : European journal of physiology · 2024Review
- Identification of TNFRSF1A as a potential biomarker for osteosarcoma.Cancer biomarkers : section A of Disease markers · 2024Article
- Acid-sensing ion channel 1a modulation of apoptosis in acidosis-related diseases: implications for therapeutic intervention.Cell death discovery · 2023Review
- Functional characterization of acid-sensing ion channels in the cerebellum-originating medulloblastoma cell line DAOY and in cerebellar granule neurons.Pflugers Archiv : European journal of physiology · 2023Article
- Aggressive migration in acidic pH of a glioblastoma cancer stem cell line in vitro is independent of ASIC and KPflugers Archiv : European journal of physiology · 2023Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Eliciting regulated cell death, like necroptosis, is a potential cancer treatment. However, pathways eliciting necroptosis are poorly understood. It has been reported that prolonged activation of acid-sensing ion channel 1a (ASIC1a) induces necroptosis in mouse neurons. Glioblastoma stem cells (GSCs) also express functional ASIC1a, but whether prolonged activation of ASIC1a induces necroptosis in GSCs is unknown. Here we used a tumorsphere formation assay to show that slight acidosis (pH 6.6) induces necrotic cell death in a manner that was sensitive to the necroptosis inhibitor Nec-1 and to the ASIC1a antagonist PcTx1. In addition, genetic knockout of ASIC1a rendered GSCs resistant to acid-induced reduction in tumorsphere formation, while the ASIC1 agonist MitTx1 reduced tumorsphere formation also at neutral pH. Finally, a 20 amino acid fragment of the ASIC1 C-terminus, thought to interact with the necroptosis kinase RIPK1, was sufficient to reduce the formation of tumorspheres. Meanwhile, the genetic knockout of MLKL, the executive protein in the necroptosis cascade, did not prevent a reduction in tumor sphere formation, suggesting that ASIC1a induced an alternative cell death pathway. These findings demonstrate that ASIC1a is a death receptor on GSCs that induces cell death during prolonged acidosis. We propose that this pathway shapes the evolution of a tumor in its acidic microenvironment and that pharmacological activation of ASIC1a might be a potential new strategy in tumor therapy.
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