ArticleOncogene2017
MDM2 but not MDM4 promotes retinoblastoma cell proliferation through p53-independent regulation of MYCN translation.
Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 44 citations in OpenAlex.
- The trends of retinoblastoma research in the past decade.International journal of ophthalmology · 2026Article
- Post-translational modifications in retinoblastoma: mechanisms, immune regulation, and therapeutic opportunities.Frontiers in immunology · 2026Review
- Tumor heterogeneity in retinoblastoma: a literature review.Cancer metastasis reviews · 2025Review
- Targeting the MYCN-MDM2 pathways for cancer therapy: Are they druggable?Genes & diseases · 2025Review
- Aurora A Kinase Inhibition Is Synthetic Lethal With the Activation of MYCN in Retinoblastoma.Investigative ophthalmology & visual science · 2025Article
- Lethal clinical outcome and chemotherapy and immunotherapy resistance in patients with urothelial carcinoma with MDM2 amplification or overexpression.Journal for immunotherapy of cancer · 2025Article
- Bringing p53 Back: A Prion-Powered Attack on Retinoblastoma.International journal of biological sciences · 2025Article
- Research Progress on the Role of Ubiquitination in Eye Diseases.Cell biochemistry and biophysics · 2024Review
- Inhibition of high level E2F in a RB1 proficient MYCN overexpressing chicken retinoblastoma model normalizes neoplastic behaviour.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- MDM2- an indispensable player in tumorigenesis.Molecular biology reports · 2023Review
- Retinoblastoma: A review of the molecular basis of tumor development and its clinical correlation in shaping future targeted treatment strategies.Indian journal of ophthalmology · 2023Review
- Article
- MDM2 promotes cancer cell survival through regulating the expression of HIF-1α and pVHL in retinoblastoma.Pathology oncology research : POR · 2023Article
- MYCN Impact on High-Risk Neuroblastoma: From Diagnosis and Prognosis to Targeted Treatment.Cancers · 2022Review
- An immature, dedifferentiated, and lineage-deconstrained cone precursor origin of N-Myc-initiated retinoblastoma.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- A high-risk retinoblastoma subtype with stemness features, dedifferentiated cone states and neuronal/ganglion cell gene expression.Nature communications · 2021Article
- The roles and regulation of MDM2 and MDMX: it is not just about p53.Genes & development · 2021Review
- Introduction of a Variant Classification System for Analysis of Genotype-Phenotype Relationships in Heritable Retinoblastoma.Cancers · 2021Article
- Molecular Changes in Retinoblastoma beyondCancers · 2021Article
- Histopathological effect of pterostilbene as chemoprevention in N-nitroso-tri-chloroethylurea (NTCU)-induced lung squamous cell carcinoma (SCC) mouse model.Histology and histopathology · 2020Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Retinoblastomas can arise from cone photoreceptor precursors in response to the loss of pRB function. Cone precursor-specific circuitry cooperates with pRB loss to initiate this process and subsequently contributes to the malignancy. Intrinsic high-level MDM2 expression is a key component of the cone precursor circuitry and is thought to inactivate p53-mediated tumor surveillance, which could otherwise be induced in response to pRB loss. However, the MDM2-related MDM4 has also been proposed to abrogate p53-mediated tumor surveillance in the absence of detectable MDM2 in retinoblastoma cells, bringing into question the importance of high-level MDM2 versus MDM4 expression. Here we report that high-level MDM2 but not MDM4 has a consistent critical role in retinoblastoma cell proliferation in vitro, as well as in orthotopic xenografts. Reduction of either MDM2 or MDM4 weakly induced p53, yet reduction of MDM2 but not MDM4 severely impaired proliferation and survival through a p53-independent mechanism. Specifically, MDM2 upregulated the mRNA expression and translation of another component of the cone circuitry, MYCN, in retinoblastoma cells. Moreover, MYCN was essential to retinoblastoma cell growth and tumor formation, and ectopic MYCN partially reversed the effects of MDM2 depletion, indicating that MYCN is an important MDM2 target. These findings indicate that high-level MDM2 expression is needed in order to perform a critical p53-independent function and may obviate the need for genomic alterations to the p53 pathway during retinoblastoma tumorigenesis.
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