ArticleNature communications2019
PPM1D mutations silence NAPRT gene expression and confer NAMPT inhibitor sensitivity in glioma.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
What it found
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Who cites it
45 citing papers in PubMed, 73 citations in OpenAlex.
- NAPRT Expression and Epigenetic Regulation in Pediatric Rhabdomyosarcoma as a Potential Biomarker for NAMPT Inhibition.Molecular cancer therapeutics · 2026Article
- NAPRT loss promotes lung tumor initiation and growth through AKT signaling independently of NADMolecular oncology · 2026Article
- OncogenicbioRxiv : the preprint server for biology · 2025Article
- Establishment of xenografts and methods to evaluate tumor burden for the three most frequent subclasses of pediatric-type diffuse high grade gliomas.Journal of neuro-oncology · 2025Article
- NAPRT Silencing in FH-Deficient Renal Cell Carcinoma Confers Therapeutic Vulnerabilities via NAD+ Depletion.Molecular cancer research : MCR · 2024Article
- Review
- Exploiting Metabolic Defects in Glioma with Nanoparticle-Encapsulated NAMPT Inhibitors.Molecular cancer therapeutics · 2024Article
- NAD in pathological cardiac remodeling: Metabolic regulation and beyond.Biochimica et biophysica acta. Molecular basis of disease · 2024Review
- Inhibitors of NADInternational journal of molecular sciences · 2024Review
- Multi-omics analysis reveals NNMT as a master metabolic regulator of metastasis in esophageal squamous cell carcinoma.NPJ precision oncology · 2024Article
- Single-cell transcriptomic analysis identifies downregulated phosphodiesterase 8B as a novel oncogene in IDH-mutant glioma.Frontiers in immunology · 2024Article
- DNMT3A mutation promotes leukemia development through NAM-NAD metabolic reprogramming.Journal of translational medicine · 2023Article
- A Compendium of Syngeneic, Transplantable Pediatric High-Grade Glioma Models Reveals Subtype-Specific Therapeutic Vulnerabilities.Cancer discovery · 2023Article
- Pyruvate transamination and NAD biosynthesis enable proliferation of succinate dehydrogenase-deficient cells by supporting aerobic glycolysis.Cell death & disease · 2023Article
- Oncohistones and disrupted development in pediatric-type diffuse high-grade glioma.Cancer metastasis reviews · 2023Review
- Preclinical validation of a novel therapeutic strategy for choroid plexus carcinoma.Journal of controlled release : official journal of the Controlled Release Society · 2023Article
- A Versatile Continuous Fluorometric Enzymatic Assay for Targeting Nicotinate Phosphoribosyltransferase.Molecules (Basel, Switzerland) · 2023Article
- Nucleic acid drug vectors for diagnosis and treatment of brain diseases.Signal transduction and targeted therapy · 2023Review
- Targeting NADFrontiers in immunology · 2023Review
- Sirtuins are Not Conserved Longevity Genes.Life metabolism · 2022Article
Corrections and comments
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Authors and funding
15 authors at 7 institutions in 2 countries.
Funding
Abstract
Pediatric high-grade gliomas are among the deadliest of childhood cancers due to limited knowledge of early driving events in their gliomagenesis and the lack of effective therapies available. In this study, we investigate the oncogenic role of PPM1D, a protein phosphatase often found truncated in pediatric gliomas such as DIPG, and uncover a synthetic lethal interaction between PPM1D mutations and nicotinamide phosphoribosyltransferase (NAMPT) inhibition. Specifically, we show that mutant PPM1D drives hypermethylation of CpG islands throughout the genome and promotes epigenetic silencing of nicotinic acid phosphoribosyltransferase (NAPRT), a key gene involved in NAD biosynthesis. Notably, PPM1D mutant cells are shown to be sensitive to NAMPT inhibitors in vitro and in vivo, within both engineered isogenic astrocytes and primary patient-derived model systems, suggesting the possible application of NAMPT inhibitors for the treatment of pediatric gliomas. Overall, our results reveal a promising approach for the targeting of PPM1D mutant tumors, and define a critical link between oncogenic driver mutations and NAD metabolism, which can be exploited for tumor-specific cell killing.
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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.