ArticleOncotarget2016
MLN4924 suppresses neddylation and induces cell cycle arrest, senescence, and apoptosis in human osteosarcoma.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 54 citations in OpenAlex.
- Neddylation: from regulatory mechanisms to clinical implications in cancer.Journal of advanced research · 2026Review
- Unbiased CRISPR synthetic lethal screening for genetic vulnerabilities in a succinate dehydrogenase-loss model of paraganglioma.iScience · 2026Article
- Complete NUB1 depletion in ER - negative breast cancer progression in paired primary-metastatic cases: a case series.Journal of medical case reports · 2026Article
- The multifaceted role of E3 ubiquitin ligases in cancer metastasis: mechanisms, targets, and therapeutic implications.Essays in biochemistry · 2025Review
- NEDDylation Regulates CD8+ T-cell Metabolism and Antitumor Immunity.Cancer immunology research · 2025Article
- Dual role of targeting NAE1 in nasopharyngeal carcinoma: Antitumor effects yet inducing radiotherapy resistance.Heliyon · 2024Article
- The Role of Ubiquitination in Osteosarcoma Development and Therapies.Biomolecules · 2024Review
- Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024Review
- Review
- Article
- Discovery of neddylation E2s inhibitors with therapeutic activity.Oncogenesis · 2023Review
- Targeting NEDD8-activating enzyme for cancer therapy: developments, clinical trials, challenges and future research directions.Journal of hematology & oncology · 2023Review
- MLN4924 Promotes Self-Renewal of Limbal Stem Cells and Ocular Surface Restoration.Journal of personalized medicine · 2023Article
- NEDD8-conjugating enzyme E2s: critical targets for cancer therapy.Cell death discovery · 2023Review
- Ubiquitin Proteasome Gene Signatures in Ependymoma Molecular Subtypes.International journal of molecular sciences · 2022Review
- Targeting Apoptosis in AML: Where Do We Stand?Cancers · 2022Review
- Pseudogene UBE2MP1 derived transcript enhancesAging · 2022Article
- Circadian rhythms and cancers: the intrinsic links and therapeutic potentials.Journal of hematology & oncology · 2022Review
- SUMOylation and NEDDylation in Primary and Metastatic Cancers to Bone.Frontiers in cell and developmental biology · 2022Review
- Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neddylation is a post-translational protein modification process associated with carcinogenesis and cancer development. MLN4924, a pharmaceutical neddylation inhibitor, induces potent anti-cancer effects in multiple types of cancers. In this study, we investigated the effects of MLN4924 on human osteosarcoma (OS). Levels of both NEDD8 activating enzyme E1 (NAE1) and ubiquitin-conjugating enzyme E2M (Ube2M), two critical components of the neddylation pathway, were much higher in OS tissues and cells than in normal osseous tissues and cells. MLN4924 treatment led to DNA damage, reduced cell viability, senescence and apoptosis in OS cells. Moreover, MLN4924 inhibited OS xenograft tumor growth in mice. Mechanistically, MLN4924 blocked the neddylation of cullins and induced accumulation of several tumor-suppressive substrates of Cullin-RING E3 ubiquitin ligases (CRLs), including CDT1, Wee1, p21, p27, Noxa, and p16. These results suggest clinical studies investigating the utility of MLN4924 for the treatment of OS are warranted.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.