ArticleJCI insight2017
Nicotinamide metabolism regulates glioblastoma stem cell maintenance.
Article in JCI insight, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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Who cites it
87 citing papers in PubMed, 137 citations in OpenAlex.
- NNMT Loss Drives Cancer Progression by enhancing SAM availability for mTORC1 Signaling and Chromatin Methylation.bioRxiv : the preprint server for biology · 2026Article
- NNMT and the methylation sink: integrating metabolism, epigenetics and immunity in cancer.BMC medicine · 2026Review
- Nicotinamide N-methyltransferase as a therapeutic target in taxane-resistant castration-resistant prostate cancer.Cell death discovery · 2026Article
- Stromal NNMT overexpression as an independent prognostic biomarker in lung adenocarcinoma and breast carcinoma.Carcinogenesis · 2026Article
- Review
- Targeting Metabolic Vulnerabilities in Glioblastoma: a Framework for Multi-node Combination Therapy.Current oncology reports · 2026Review
- Steroid-dependent metabolic rewiring reveals novel therapeutic and imaging approaches for glioblastoma.Science advances · 2026Article
- Explore the Heterogeneity of Glioblastoma Based on Genes Related to Glutamine Metabolism.Cancer informatics · 2026Article
- NAD Metabolism Regulates Proliferation of Macrophages in Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- ODC-Driven Polyamines Synthesis Sustains the Self-Renewal of Glioblastoma Stem Cells and Drives Tumor Aggressiveness.Cancer science · 2025Article
- Phenotypic variations in glioma stem cells: regulatory mechanisms and implications for therapeutic strategies.Journal of translational medicine · 2025Review
- Towards non-invasive diagnosis of glioblastoma: identifying metabolic biomarkers in liquid biopsies using a ROC-based approach.Discover oncology · 2025Article
- Glioma promotes macrophage immunosuppressive phenotype through ANXA1 in a methionine metabolism-dependent manner.Discover oncology · 2025Article
- Epigenetic Alterations in Glioblastoma Multiforme as Novel Therapeutic Targets: A Scoping Review.International journal of molecular sciences · 2025Article
- Nicotinamide metabolism reprogramming drives reversible senescence of glioblastoma cells.Cellular and molecular life sciences : CMLS · 2025Article
- Article
- Heterogeneous DNA methylation and gene expression patterns underly metabolic plasticity in canine astrocytoma-derived stem-like cells.Frontiers in oncology · 2025Article
- MAT2a and AHCY inhibition disrupts antioxidant metabolism and reduces glioblastoma cell survival.bioRxiv : the preprint server for biology · 2024Article
- Metabolic regulation of the glioblastoma stem cell epitranscriptome by malate dehydrogenase 2.Cell metabolism · 2024Article
- Vitamin B6 Pathway Maintains Glioblastoma Cell Survival in 3D Spheroid Cultures.International journal of molecular sciences · 2024Article
27 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
11 authors at 2 institutions in 1 country.
Funding
Abstract
Metabolic dysregulation promotes cancer growth through not only energy production, but also epigenetic reprogramming. Here, we report that a critical node in methyl donor metabolism, nicotinamide N-methyltransferase (NNMT), ranked among the most consistently overexpressed metabolism genes in glioblastoma relative to normal brain. NNMT was preferentially expressed by mesenchymal glioblastoma stem cells (GSCs). NNMT depletes S-adenosyl methionine (SAM), a methyl donor generated from methionine. GSCs contained lower levels of methionine, SAM, and nicotinamide, but they contained higher levels of oxidized nicotinamide adenine dinucleotide (NAD+) than differentiated tumor cells. In concordance with the poor prognosis associated with DNA hypomethylation in glioblastoma, depletion of methionine, a key upstream methyl group donor, shifted tumors toward a mesenchymal phenotype and accelerated tumor growth. Targeting NNMT expression reduced cellular proliferation, self-renewal, and in vivo tumor growth of mesenchymal GSCs. Supporting a mechanistic link between NNMT and DNA methylation, targeting NNMT reduced methyl donor availability, methionine levels, and unmethylated cytosine, with increased levels of DNA methyltransferases, DNMT1 and DNMT3A. Supporting the clinical significance of these findings, NNMT portended poor prognosis for glioblastoma patients. Collectively, our findings support NNMT as a GSC-specific therapeutic target in glioblastoma by disrupting oncogenic DNA hypomethylation.
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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.