ArticleCell death & disease2019
Combinatorial targeting of MTHFD2 and PAICS in purine synthesis as a novel therapeutic strategy.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- A five-gene TAM and MYCN signature predicts prognosis and identifies MTHFD2 as a therapeutic target in neuroblastoma.Discover oncology · 2026Article
- MTHFD2: a promising metabolic checkpoint for diseases.Journal of translational medicine · 2026Review
- MTHFD2 is required for DNA repair and implicated in LUAD radiotherapy resistance.Journal of translational medicine · 2026Article
- Review
- Inhibition of Purine Metabolism Promotes the Differentiation of Neuroblastoma Driven by MYCN.Cancer medicine · 2025Article
- Therapeutic targeting de novo purine biosynthesis driven by β-catenin-dependent PPAT upregulation in hepatoblastoma.Cell death & disease · 2025Article
- Introducing New Inhibitors of PAICS, aIranian journal of biotechnology · 2025Article
- The one-carbon metabolic enzyme MTHFD2 promotes resection and homologous recombination after ionizing radiation.Molecular oncology · 2024Article
- MTHFD2 in healthy and cancer cells: Canonical and non-canonical functions.npj metabolic health and disease · 2024Review
- MTHFD1 regulates the NADPH redox homeostasis in MYCN-amplified neuroblastoma.Cell death & disease · 2024Article
- Targeting the DNA damage response and repair in cancer through nucleotide metabolism.Molecular oncology · 2022Review
- MYCN and Metabolic Reprogramming in Neuroblastoma.Cancers · 2022Review
- Reaction Mechanism of Human PAICS Elucidated by Quantum Chemical Calculations.Journal of the American Chemical Society · 2022Article
- Deacetylation of MTHFD2 by SIRT4 senses stress signal to inhibit cancer cell growth by remodeling folate metabolism.Journal of molecular cell biology · 2022Article
- EIF4EBP1 is transcriptionally upregulated by MYCN and associates with poor prognosis in neuroblastoma.Cell death discovery · 2022Article
- Study on the role of transcription factor SPI1 in the development of glioma.Chinese neurosurgical journal · 2022Article
- ATF4/MYC Regulates MTHFD2 to Promote NSCLC Progression by Mediating Redox Homeostasis.Disease markers · 2022Article
- Serine and one-carbon metabolisms bring new therapeutic venues in prostate cancer.Discover oncology · 2021Review
- Review
- Crystal structures of human PAICS reveal substrate and product binding of an emerging cancer target.The Journal of biological chemistry · 2020Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
MYCN-amplified (MNA) neuroblastoma is an aggressive neural crest-derived pediatric cancer. However, MYCN is indispensable for development and transcriptionally regulates extensive network of genes. Integrating anti-MYCN ChIP-seq and gene expression profiles of neuroblastoma patients revealed the metabolic enzymes, MTHFD2 and PAICS, required for one-carbon metabolism and purine biosynthesis were concomitantly upregulated, which were more susceptible to metastatic neuroblastoma. Moreover, we found that MYCN mediated the folate cycle via MTHFD2, which contributed one-carbon unit to enhance purine synthesis, and further regulated nucleotide production by PAICS in response to cancer progression. Dual knockdown of the MYCN-targeted gene pair, MTHFD2 and PAICS, in MNA neuroblastoma cells synergically reduced cell proliferation, colony formation, migration ability, and DNA synthesis. By systematically screening the compound perturbagens, the gene expression levels of MTHFD2 and PAICS were specifically suppressed by anisomycin and apicidin across cell lines, and our co-treatment results also displayed synergistic inhibition of MNA neuroblastoma cell proliferation. Collectively, targeting a combination of MYCN-targeted genes that interrupts the interconnection of metabolic pathways may overcome drug toxicity and improve the efficacy of current therapeutic agents in MNA neuroblastoma.
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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.