ArticleOncotarget2015
MYCN amplification confers enhanced folate dependence and methotrexate sensitivity in neuroblastoma.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- Beta-cyclodextrin-based polymerized nanocarriers for doxorubicin delivery to cancer cells.Nanoscale advances · 2026Article
- Review
- Identification of locally advanced rectal cancer-related genes based on transcriptome and mendelian randomization analysis with biological validation.Frontiers in immunology · 2025Article
- MTHFD1 regulates the NADPH redox homeostasis in MYCN-amplified neuroblastoma.Cell death & disease · 2024Article
- Impact of genetic variants in the solute carrier (Cancer drug resistance (Alhambra, Calif.) · 2024Review
- Application of the FISH method and high-density SNP arrays to assess genetic changes in neuroblastoma-research by one institute.Acta biochimica Polonica · 2024Article
- The Role of Solute Carrier Transporters in Efficient Anticancer Drug Delivery and Therapy.Pharmaceutics · 2023Review
- DDA-SKF: Predicting Drug-Disease Associations Using Similarity Kernel Fusion.Frontiers in pharmacology · 2021Review
- Preclinical evaluation of the anti-tumor activity of pralatrexate in high-risk neuroblastoma cells.Oncotarget · 2020Article
- Thymidylate synthase inhibitor raltitrexed can induce high levels of DNA damage in MYCN-amplified neuroblastoma cells.Cancer science · 2020Article
- Metabolic Reprogramming by MYCN Confers Dependence on the Serine-Glycine-One-Carbon Biosynthetic Pathway.Cancer research · 2019Article
- A sketch of known and novel MYCN-associated miRNA networks in neuroblastoma.Oncology reports · 2017Article
- Article
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
MYCN amplification occurs in 20% of neuroblastomas and is strongly related to poor clinical outcome. We have identified folate-mediated one-carbon metabolism as highly upregulated in neuroblastoma tumors with MYCN amplification and have validated this finding experimentally by showing that MYCN amplified neuroblastoma cell lines have a higher requirement for folate and are significantly more sensitive to the antifolate methotrexate than cell lines without MYCN amplification. We have demonstrated that methotrexate uptake in neuroblastoma cells is mediated principally by the reduced folate carrier (RFC; SLC19A1), that SLC19A1 and MYCN expression are highly correlated in both patient tumors and cell lines, and that SLC19A1 is a direct transcriptional target of N-Myc. Finally, we assessed the relationship between SLC19A1 expression and patient survival in two independent primary tumor cohorts and found that SLC19A1 expression was associated with increased risk of relapse or death, and that SLC19A1 expression retained prognostic significance independent of age, disease stage and MYCN amplification. This study adds upregulation of folate-mediated one-carbon metabolism to the known consequences of MYCN amplification, and suggests that this pathway might be targeted in poor outcome tumors with MYCN amplification and high SLC19A1 expression.
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