ArticleCell death & disease2020
MYC transcription activation mediated by OCT4 as a mechanism of resistance to 13-cisRA-mediated differentiation in neuroblastoma.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 32 citations in OpenAlex.
- Pathology of peripheral neuroblastic tumors.Diagnostic pathology · 2026Review
- Evaluation of the anti-leukemia activity and underlying mechanisms of the novel perinucleolar compartment inhibitor CTI-2 in acute myeloid leukemia.Investigational new drugs · 2025Article
- Unlocking the Role of OCT4 in Cancer Lineage Plasticity: A Cross-Cancer Perspective with an Emphasis on Prostate Cancer.Biomedicines · 2025Review
- Peripheral neuroblastic tumors behaving badly: an update on high-risk morphologic and molecular groupings.Virchows Archiv : an international journal of pathology · 2025Review
- Molecular and phenotypic characterization of 5-FU resistant colorectal cancer cells: toward enrichment of cancer stem cells.Cancer cell international · 2025Article
- Evaluation of the anti-leukemia activity and underlying mechanisms of the novel perinucleolar compartment inhibitor CTI-2 in acute myeloid leukemia.Investigational new drugs · 2025Article
- Inhibition of OCT4 binding at theFrontiers in oncology · 2024Article
- Mitoribosomal synthetic lethality overcomes multidrug resistance in MYC-driven neuroblastoma.Cell death & disease · 2023Article
- Identification of a novel gene signature for neuroblastoma differentiation using a Boolean implication network.Genes, chromosomes & cancer · 2023Article
- DNA-PKcs as an upstream mediator of OCT4-induced MYC activation in small cell lung cancer.Biochimica et biophysica acta. Gene regulatory mechanisms · 2023Article
- MUC15 is an independent prognostic factor that promotes metastases of MYCN non-amplified neuroblastoma.Journal of Cancer · 2023Article
- Oct4 cooperates with c-Myc to improve mesenchymal-to-endothelial transition and myocardial repair of cardiac-resident mesenchymal stem cells.Stem cell research & therapy · 2022Article
- Knockdown of NRMT enhances sensitivity of retinoblastoma cells to cisplatin through upregulation of the CENPA/Myc/Bcl2 axis.Cell death discovery · 2022Article
- Genetic and Histopathological Heterogeneity of Neuroblastoma and Precision Therapeutic Approaches for Extremely Unfavorable Histology Subgroups.Biomolecules · 2022Review
- Retinoic acid rewires the adrenergic core regulatory circuitry of childhood neuroblastoma.Science advances · 2021Article
- Development of cell-based high throughput luminescence assay for drug discovery in inhibiting OCT4/DNA-PKcs and OCT4-MK2 interactions.Biotechnology and bioengineering · 2021Article
- Targeting MYCN in Molecularly Defined Malignant Brain Tumors.Frontiers in oncology · 2020Review
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Despite the improvement in clinical outcome with 13-cis-retinoic acid (13-cisRA) + anti-GD2 antibody + cytokine immunotherapy given in first response ~40% of high-risk neuroblastoma patients die of recurrent disease. MYCN genomic amplification is a biomarker of aggressive tumors in the childhood cancer neuroblastoma. MYCN expression is downregulated by 13-cisRA, a differentiating agent that is a component of neuroblastoma therapy. Although MYC amplification is rare in neuroblastoma at diagnosis, we report transcriptional activation of MYC medicated by the transcription factor OCT4, functionally replacing MYCN in 13-cisRA-resistant progressive disease neuroblastoma in large panels of patient-derived cell lines and xenograft models. We identified novel OCT4-binding sites in the MYC promoter/enhancer region that regulated MYC expression via phosphorylation by MAPKAPK2 (MK2). OCT4 phosphorylation at the S111 residue by MK2 was upstream of MYC transcriptional activation. Expression of OCT4, MK2, and c-MYC was higher in progressive disease relative to pre-therapy neuroblastomas and was associated with inferior patient survival. OCT4 or MK2 knockdown decreased c-MYC expression and restored the sensitivity to 13-cisRA. In conclusion, we demonstrated that high c-MYC expression independent of genomic amplification is associated with disease progression in neuroblastoma. MK2-mediated OCT4 transcriptional activation is a novel mechanism for activating the MYC oncogene in progressive disease neuroblastoma that provides a therapeutic target.
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