ArticleThe Journal of biological chemistry2015
Identification and pharmacological inactivation of the MYCN gene network as a therapeutic strategy for neuroblastic tumor cells.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 48 citations in OpenAlex.
- CDK2 inhibition promotes neuronal differentiation in neuroblastoma.Scientific reports · 2026Article
- A novel role for Neurog2 in MYCN driven neuroendocrine plasticity of prostate cancer.Oncogene · 2025Article
- Inhibition of AHCY impedes proliferation and differentiation of mouse and human adipocyte progenitor cells.Adipocyte · 2024Article
- Key Proteins of Replication Stress Response and Cell Cycle Control as Cancer Therapy Targets.International journal of molecular sciences · 2024Review
- Review of T cell proliferation regulatory factors in treatment and prognostic prediction for solid tumors.Heliyon · 2023Review
- Chelators as Antineuroblastomas Agents.Physiological research · 2023Article
- Single-cell next-generation sequencing of circulating tumor cells in patients with neuroblastoma.Cancer science · 2023Article
- Signature literature review reveals AHCY, DPYSL3, and NME1 as the most recurrent prognostic genes for neuroblastoma.BioData mining · 2023Article
- MGL S3 Chimeric Enzyme Drives Apoptotic Death of EGFR-Dependent Cancer Cells through ERK Downregulation.International journal of molecular sciences · 2022Article
- c-Myb-mediated inhibition of miR-601 in facilitating malignance of osteosarcoma via augmentation of PKMYT1.Scientific reports · 2022Article
- A novel T-cell proliferation-associated regulator signature pre-operatively predicted the prognostic of bladder cancer.Frontiers in immunology · 2022Article
- Identification and Characterization of a Glucometabolic Prognostic Gene Signature in Neuroblastoma based on N6-methyladenosine Eraser ALKBH5.Journal of Cancer · 2022Article
- The DNA damage repair-related geneTranslational lung cancer research · 2021Article
- A combination of PARP and CHK1 inhibitors efficiently antagonizes MYCN-driven tumors.Oncogene · 2021Article
- Ketogenesis impact on liver metabolism revealed by proteomics of lysine β-hydroxybutyrylation.Cell reports · 2021Article
- Functional and Pathological Roles of AHCY.Frontiers in cell and developmental biology · 2021Review
- A WEE1 family business: regulation of mitosis, cancer progression, and therapeutic target.Journal of hematology & oncology · 2020Review
- Repurposing a psychoactive drug for children with cancer: p27Oncogenesis · 2020Article
- Targeting the DNA Damage Response for the Treatment of High Risk Neuroblastoma.Frontiers in oncology · 2020Review
- Chromatin capture links the metabolic enzyme AHCY to stem cell proliferation.Science advances · 2019Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The MYC family of transcription factors consists of three well characterized members, c-MYC, L-MYC, and MYCN, deregulated in the majority of human cancers. In neuronal tumors such as neuroblastoma, MYCN is frequently activated by gene amplification, and reducing its expression by RNA interference has been shown to promote growth arrest and apoptosis of tumor cells. From a clinical perspective, RNA interference is not yet a viable option, and small molecule inhibitors of transcription factors are difficult to develop. We therefore planned to identify, at the global level, the genes interacting functionally with MYCN required to promote fitness of tumor cells facing oncogenic stress. To find genes whose inactivation is synthetically lethal to MYCN, we implemented a genome-wide approach in which we carried out a drop-out shRNA screen using a whole genome library that was delivered into isogenic neuroblastoma cell lines expressing or not expressing MYCN. After the screen, we selected for in-depth analysis four shRNAs targeting AHCY, BLM, PKMYT1, and CKS1B. These genes were chosen because they are directly regulated by MYC proteins, associated with poor prognosis of neuroblastoma patients, and inhibited by small molecule compounds. Mechanistically, we found that BLM and PKMYT1 are required to limit oncogenic stress and promote stabilization of the MYCN protein. Cocktails of small molecule inhibitors of CKS1B, AHCY, BLM, and PKMYT1 profoundly affected the growth of all neuroblastoma cell lines but selectively caused death of MYCN-amplified cells. Our findings suggest that drugging the MYCN network is a promising avenue for the treatment of high risk, neuroblastic cancers.
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