ArticleThe Journal of clinical investigation2020
HDAC inhibitors elicit metabolic reprogramming by targeting super-enhancers in glioblastoma models.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 137 papers, 1 of them a synthesis that pooled it.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
137 citing papers in PubMed, 1 synthesis or guideline pooled it, 202 citations in OpenAlex.
- Epigenetic Underpinnings of Inflammation: A Key to Unlock the Tumor Microenvironment in Glioblastoma.Frontiers in immunology · 2022Pooled it
- Effects of copper overload on mitochondrial parameters in GBM-1, U-87 MG, and C6 glioma cell lines.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Article
- Re-expression of MHC-I to treat CNS cancers.Oncotarget · 2026Review
- From cell to disease: Regulatory networks and mechanisms of super‑enhancers in aging (Review).Molecular medicine reports · 2026Review
- Gut-Derived Sodium Butyrate Attenuates Liver Fibrosis by Inhibiting Aerobic Glycolysis via the HDAC3/c-Myc Signaling Axis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Pharmacological chromatin remodeling enhances response to estrogen therapy in ERMolecular oncology · 2026Article
- Mechanistic insights into TXNDC17-mediated ferroptosis suppression in glioblastoma progression.Biology direct · 2026Article
- Multi-Omics Insights Into the Mechanisms of Early Muscle Fiber Difference and Transformation Between Lean-Type and Chinese Indigenous Pigs.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Large-scale and high-resolution mass spectrometry-based proteomics defines molecular subtypes of nasopharyngeal carcinoma for therapeutic targeting.Signal transduction and targeted therapy · 2026Article
- The impactful role of the HDACs in the regulation of gene expression and as targets for disease therapy.Science advances · 2026Review
- HDAC inhibition reprograms stem cell fate to suppress infantile hemangioma vasculogenesis.Angiogenesis · 2026Article
- Targeting SCAMP2 by a natural product auxarconjugatin B for glioblastoma therapyActa pharmaceutica Sinica. B · 2026Article
- The role and therapeutic potential of succinate and succinylation in cardiovascular diseases.Clinical epigenetics · 2026Review
- Disengaging the Engine: Histone Deacetylases 1 and 2-Mediated Acetylation of Hexokinase-2 Regulates Energy Metabolism in Microglia Following Intracerebral Hemorrhage.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Chromatin Accessibility in Cancer: Biological Functions, Mechanisms, Therapeutic Potential, and Future Directions.MedComm · 2026Review
- IDH-mutant inhibitors enhance the sensitivity of IDH1-mutant gliomas to cysteine-methionine deprivation and ferroptosis.bioRxiv : the preprint server for biology · 2026Article
- Lipid metabolic plasticity in glioblastoma: mechanisms, tumor microenvironment remodeling, and therapeutic opportunities.Frontiers in oncology · 2026Review
- Identification and targeting oxidative phosphorylation/glycolysis to overcome anti-CSF-1R therapy resistance in glioblastoma.Cell death & disease · 2025Article
- CDK12 regulates cellular metabolism to promote glioblastoma growth.JCI insight · 2025Article
- Irisin deficiency exacerbates cardiac dysfunction and enhances hemorrhage injury in hemorrhage/resuscitation.American journal of physiology. Regulatory, integrative and comparative physiology · 2025Article
77 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
19 authors at 6 institutions in 2 countries.
Funding
Abstract
The Warburg effect is a tumor-related phenomenon that could potentially be targeted therapeutically. Here, we showed that glioblastoma (GBM) cultures and patients' tumors harbored super-enhancers in several genes related to the Warburg effect. By conducting a transcriptome analysis followed by ChIP-Seq coupled with a comprehensive metabolite analysis in GBM models, we found that FDA-approved global (panobinostat, vorinostat) and selective (romidepsin) histone deacetylase (HDAC) inhibitors elicited metabolic reprogramming in concert with disruption of several Warburg effect-related super-enhancers. Extracellular flux and carbon-tracing analyses revealed that HDAC inhibitors blunted glycolysis in a c-Myc-dependent manner and lowered ATP levels. This resulted in the engagement of oxidative phosphorylation (OXPHOS) driven by elevated fatty acid oxidation (FAO), rendering GBM cells dependent on these pathways. Mechanistically, interference with HDAC1/-2 elicited a suppression of c-Myc protein levels and a concomitant increase in 2 transcriptional drivers of oxidative metabolism, PGC1α and PPARD, suggesting an inverse relationship. Rescue and ChIP experiments indicated that c-Myc bound to the promoter regions of PGC1α and PPARD to counteract their upregulation driven by HDAC1/-2 inhibition. Finally, we demonstrated that combination treatment with HDAC and FAO inhibitors extended animal survival in patient-derived xenograft model systems in vivo more potently than single treatments in the absence of toxicity.
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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.