ArticleCancer research2023
Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma.
Article in Cancer research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 28 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Treatment-induced ripple effect: a systematic review exploring the abscopal phenomenon in Glioblastoma multiforme.Journal of neuro-oncology · 2025Pooled it
- Narcolepsy is (not) an autoimmune disease.Nature reviews. Neurology · 2026Review
- HOXC9 enhances cholesterol metabolism and malignancy in pancreatic ductal adenocarcinoma through ITGA10/FAK/PI3K/CREB-dependent HMGCR activation.Journal of gastroenterology · 2026Article
- Beyond energy production: targeting mitochondrial biogenesis in aging and cancer with phytochemical intervention.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Discovery of Niclosamide Analogs with Potent Mitochondrial Uncoupling Activity and Reduced Mitochondrial Inhibition-Associated Toxicity.ACS medicinal chemistry letters · 2026Article
- Mitochondrial uncoupling inhibits serine catabolismCancer biology & medicine · 2026Article
- GFPT2 drives sunitinib resistance of renal cell carcinoma via enzyme-dependent and -independent manners.International journal of biological sciences · 2026Article
- Epigenetic crosstalk in neuroblastoma development and progression.Frontiers in cell and developmental biology · 2026Review
- Niclosamide suppresses gastric cancer progression through YTHDF2 inhibition-affected lactate metabolic reprogramming.iScience · 2025Article
- Restoring mitochondrial quantity and quality to reverse the Warburg effect and drive neuroblastoma differentiation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Valine-Niclosamide for Treatment of Androgen Receptor Splice Variant-Positive Hepatocellular Carcinoma.Cancers · 2025Article
- A Strategic Antimetastatic Solution for Bone-Targeting Prostate Cancer via Nanoengineered Niclosamide.Nano letters · 2025Review
- Development of a prognostic model for overall survival in neuroblastoma based on Schwann cell-specific genes, clinical predictors, and MYCN amplification.Translational cancer research · 2025Article
- Bridging epigenomics and tumor immunometabolism: molecular mechanisms and therapeutic implications.Molecular cancer · 2025Review
- Mitochondrial uncouplers inhibit oncogenic E2F1 activity and prostate cancer growth.Cell reports. Medicine · 2025Article
- Central nervous system and immune cells interactions in cancer: unveiling new therapeutic avenues.Frontiers in immunology · 2025Review
- Exploring the oncogenic impact of heteroplasmicMitochondrial communications · 2025Article
- Molecular regulation and therapeutic targeting ofFrontiers in cell and developmental biology · 2025Review
- Defining neuroblastoma: From origin to precision medicine.Neuro-oncology · 2024Review
- The Warburg effect drives dedifferentiation through epigenetic reprogramming.Cancer biology & medicine · 2024Article
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
19 authors at 4 institutions in 1 country.
Funding
Abstract
The Warburg effect is the major metabolic hallmark of cancer. According to Warburg himself, the consequence of the Warburg effect is cell dedifferentiation. Therefore, reversing the Warburg effect might be an approach to restore cell differentiation in cancer. In this study, we used a mitochondrial uncoupler, niclosamide ethanolamine (NEN), to activate mitochondrial respiration, which induced neural differentiation in neuroblastoma cells. NEN treatment increased the NAD+/NADH and pyruvate/lactate ratios and also the α-ketoglutarate/2-hydroxyglutarate (2-HG) ratio. Consequently, NEN treatment induced promoter CpG island demethylation and epigenetic landscape remodeling, activating the neural differentiation program. In addition, NEN treatment upregulated p53 but downregulated N-Myc and β-catenin signaling in neuroblastoma cells. Importantly, even under hypoxia, NEN treatment remained effective in inhibiting 2-HG generation, promoting DNA demethylation, and suppressing hypoxia-inducible factor signaling. Dietary NEN intervention reduced tumor growth rate, 2-HG levels, and expression of N-Myc and β-catenin in tumors in an orthotopic neuroblastoma mouse model. Integrative analysis indicated that NEN treatment upregulated favorable prognosis genes and downregulated unfavorable prognosis genes, which were defined using multiple neuroblastoma patient datasets. Altogether, these results suggest that mitochondrial uncoupling is an effective metabolic and epigenetic therapy for reversing the Warburg effect and inducing differentiation in neuroblastoma. SIGNIFICANCE: Targeting cancer metabolism using the mitochondrial uncoupler niclosamide ethanolamine leads to methylome reprogramming and differentiation in neuroblastoma, providing a therapeutic opportunity to reverse the Warburg effect and suppress tumor growth. See related commentary by Byrne and Bell, p.167.
Indexed as
Identifiers
What OpenQuestion holds
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.