ArticleActa neuropathologica2017
A driver role for GABA metabolism in controlling stem and proliferative cell state through GHB production in glioma.
Article in Acta neuropathologica, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 73 citations in OpenAlex.
- Human cerebral organoids with microglia and vasculature model glioma stem cell interactions and radiotherapy response.Cell reports methods · 2026Article
- Neurotransmitter-Mediated Signaling in Glioblastoma and Glial Tumors: Biology and Therapeutic Opportunities.Oncology research · 2026Review
- Neurotransmitter Regulatory Networks: A New Perspective on Cancer Therapy.Biomolecules · 2025Review
- ALDH2 in autophagy and cell death: molecular mechanisms and implications for diseases.Military Medical Research · 2025Review
- The excitatory milieu in glioma: Mechanisms and therapeutic avenues.Neuro-oncology · 2025Review
- GABAergic Influences on Medulloblastoma.Brain sciences · 2025Review
- Universal multilayer network embedding reveals a causal link between GABA neurotransmitter and cancer.BMC bioinformatics · 2025Article
- Nicotinamide metabolism reprogramming drives reversible senescence of glioblastoma cells.Cellular and molecular life sciences : CMLS · 2025Article
- Advancements in Valproate Therapy for Seizures, Migraines, and Bipolar Disorders.Medical principles and practice : international journal of the Kuwait University, Health Science Centre · 2025Review
- Article
- Transgelin Promotes Glioblastoma Stem Cell Hypoxic Responses and Maintenance Through p53 Acetylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Article
- Proteome-wide Mendelian randomization identifies therapeutic targets for ankylosing spondylitis.Frontiers in immunology · 2024Article
- CaMKK2 as an emerging treatment target for bipolar disorder.Molecular psychiatry · 2023Review
- CELF2 Sustains a Proliferating/OLIG2+ Glioblastoma Cell Phenotype via the Epigenetic Repression of SOX3.Cancers · 2023Article
- Glioma Cells Expressing High Levels of ALDH5A1 Exhibit Enhanced Migration Transcriptional Signature in Patient Tumors.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Article
- Aldehyde dehydrogenase in solid tumors and other diseases: Potential biomarkers and therapeutic targets.MedComm · 2023Review
- Proteomics reveals differentially regulated pathways when comparing grade 2 and 4 astrocytomas.PloS one · 2023Article
- Glioblastoma cell motility depends on enhanced oxidative stress coupled with mobilization of a sulfurtransferase.Cell death & disease · 2022Article
- Neurotransmitters: Potential Targets in Glioblastoma.Cancers · 2022Review
Corrections and comments
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Authors and funding
30 authors at 15 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cell populations with differing proliferative, stem-like and tumorigenic states co-exist in most tumors and especially malignant gliomas. Whether metabolic variations can drive this heterogeneity by controlling dynamic changes in cell states is unknown. Metabolite profiling of human adult glioblastoma stem-like cells upon loss of their tumorigenicity revealed a switch in the catabolism of the GABA neurotransmitter toward enhanced production and secretion of its by-product GHB (4-hydroxybutyrate). This switch was driven by succinic semialdehyde dehydrogenase (SSADH) downregulation. Enhancing GHB levels via SSADH downregulation or GHB supplementation triggered cell conversion into a less aggressive phenotypic state. GHB affected adult glioblastoma cells with varying molecular profiles, along with cells from pediatric pontine gliomas. In all cell types, GHB acted by inhibiting α-ketoglutarate-dependent Ten-eleven Translocations (TET) activity, resulting in decreased levels of the 5-hydroxymethylcytosine epigenetic mark. In patients, low SSADH expression was correlated with high GHB/α-ketoglutarate ratios, and distinguished weakly proliferative/differentiated glioblastoma territories from proliferative/non-differentiated territories. Our findings support an active participation of metabolic variations in the genesis of tumor heterogeneity.
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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.