ArticleMolecular oncology2016
Glutathione biosynthesis is upregulated at the initiation of MYCN-driven neuroblastoma tumorigenesis.
Article in Molecular oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 26 citations in OpenAlex.
- Review
- Molecular regulation and therapeutic targeting ofFrontiers in cell and developmental biology · 2025Review
- Mitotic Dysregulation at Tumor Initiation Creates a Therapeutic Vulnerability to Combination Anti-Mitotic and Pro-Apoptotic Agents for MYCN-Driven Neuroblastoma.International journal of molecular sciences · 2023Article
- DHODH is an independent prognostic marker and potent therapeutic target in neuroblastoma.JCI insight · 2022Article
- Targeting lipid metabolism in cancer: neuroblastoma.Cancer metastasis reviews · 2022Review
- Article
- Article
- Inhibition of fatty acid synthesis induces differentiation and reduces tumor burden in childhood neuroblastoma.iScience · 2021Article
- Identification of Pre-Diagnostic Metabolic Patterns for Glioma Using Subset Analysis of Matched Repeated Time Points.Cancers · 2020Article
- The liposomal delivery of hydrophobic oxidovanadium complexes imparts highly effective cytotoxicity and differentiating capacity in neuroblastoma tumour cells.Scientific reports · 2020Article
- Article
- The NRF2/KEAP1 Axis in the Regulation of Tumor Metabolism: Mechanisms and Therapeutic Perspectives.Biomolecules · 2020Review
- Potential Applications of NRF2 Modulators in Cancer Therapy.Antioxidants (Basel, Switzerland) · 2020Review
- MYCN and PRC1 cooperatively repress docosahexaenoic acid synthesis in neuroblastoma via ELOVL2.Journal of experimental & clinical cancer research : CR · 2019Article
- Combinatorial targeting of MTHFD2 and PAICS in purine synthesis as a novel therapeutic strategy.Cell death & disease · 2019Article
- Disrupting Mitochondrial Pyruvate Uptake Directs Glutamine into the TCA Cycle away from Glutathione Synthesis and Impairs Hepatocellular Tumorigenesis.Cell reports · 2019Article
- Short overview on metabolomics approach to study pathophysiology of oxidative stress in cancer.Redox biology · 2018Review
- The MYCN Protein in Health and Disease.Genes · 2017Review
- Review
- [Clinical features and outcomes of neuroblastoma patients aged above 5 years].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2016Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The MYCN gene is amplified and overexpressed in a large proportion of high stage neuroblastoma patients and has been identified as a key driver of tumorigenesis. However, the mechanism by which MYCN promotes tumor initiation is poorly understood. Here we conducted metabolic profiling of pre-malignant sympathetic ganglia and tumors derived from the TH-MYCN mouse model of neuroblastoma, compared to non-malignant ganglia from wildtype littermates. We found that metabolites involved in the biosynthesis of glutathione, the most abundant cellular antioxidant, were the most significantly upregulated metabolic pathway at tumor initiation, and progressively increased to meet the demands of tumorigenesis. A corresponding increase in the expression of genes involved in ribosomal biogenesis suggested that MYCN-driven transactivation of the protein biosynthetic machinery generated the necessary substrates to drive glutathione biosynthesis. Pre-malignant sympathetic ganglia from TH-MYCN mice had higher antioxidant capacity and required glutathione upregulation for cell survival, when compared to wildtype ganglia. Moreover, in vivo administration of inhibitors of glutathione biosynthesis significantly delayed tumorigenesis when administered prophylactically and potentiated the anticancer activity of cytotoxic chemotherapy against established tumors. Together these results identify enhanced glutathione biosynthesis as a selective metabolic adaptation required for initiation of MYCN-driven neuroblastoma, and suggest that glutathione-targeted agents may be used as a potential preventative strategy, or as an adjuvant to existing chemotherapies in established disease.
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