ArticleNeuro-oncology2015
Suppression of glioblastoma by targeting the overactivated protein neddylation pathway.
Erratum issuedOpen access · bronzeAbstract read
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Article in Neuro-oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 52 papers.
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52citing papers in PubMed
2.3field-weighted citation impact, top 12% of its field
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Who cites it
52 citing papers in PubMed, 88 citations in OpenAlex.
- Protein neddylation as a therapeutic target: challenges and opportunities.The Journal of clinical investigation · 2026Review
- Neddylation: from regulatory mechanisms to clinical implications in cancer.Journal of advanced research · 2026Review
- UBE2M as a bridge spanning neddylation and cell cycle regulation in colorectal adenocarcinoma.Experimental & molecular medicine · 2026Article
- Decoding neddylation in malignancies: molecular mechanisms, biological functions, therapeutic resistance, and clinical potential.Cell death & disease · 2026Review
- CUL4B promotes hepatocellular carcinoma progression and oxaliplatin resistance by facilitating FUS degradation.Cell death & disease · 2025Article
- Transcriptome-based screening in TARDBP/TDP-43 knock-in motor neurons identifies the NEDD8-activating enzyme inhibitor MLN4924.Scientific reports · 2025Article
- Inhibiting neddylation: A new strategy for tumor therapy.Journal of pharmaceutical analysis · 2025Review
- Mapping chromatin remodelling in glioblastoma identifies epigenetic regulation of key molecular pathways and novel druggable targets.BMC biology · 2025Article
- Phase 1 study of NEDD8 activating enzyme inhibitor pevonedistat in combination with chemotherapy in pediatric patients with recurrent or refractory solid tumors (ADVL1615).European journal of cancer (Oxford, England : 1990) · 2024Article
- The Roles of AGTRAP, ALKBH3, DIVERSIN, NEDD8 and RRM1 in Glioblastoma Pathophysiology and Prognosis.Biomedicines · 2024Article
- Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024Review
- Neddylation suppression by a macrophage membrane-coated nanoparticle promotes dual immunomodulatory repair of diabetic wounds.Bioactive materials · 2024Article
- Neddylation of protein, a new strategy of protein post-translational modification for targeted treatment of central nervous system diseases.Frontiers in neuroscience · 2024Review
- Genes of the Ubiquitin Proteasome System Qualify as Differential Markers in Malignant Glioma of Astrocytic and Oligodendroglial Origin.Cellular and molecular neurobiology · 2023Review
- A Promising Way to Overcome Temozolomide Resistance through Inhibition of Protein Neddylation in Glioblastoma Cell Lines.International journal of molecular sciences · 2023Article
- Arctigenin impairs UBC12 enzyme activity and cullin neddylation to attenuate cancer cells.Acta pharmacologica Sinica · 2023Article
- NEDD8-conjugating enzyme E2s: critical targets for cancer therapy.Cell death discovery · 2023Review
- Targeting cullin neddylation for cancer and fibrotic diseases.Theranostics · 2023Review
- Ubiquitin Proteasome Gene Signatures in Ependymoma Molecular Subtypes.International journal of molecular sciences · 2022Review
- Inhibition of NEDD8 NEDDylation induced apoptosis in acute myeloid leukemia cells via p53 signaling pathway.Bioscience reports · 2022Article
Corrections and comments
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- Erratum issued
Authors and funding
14 authors at 8 institutions in 2 countries.
Wei HuaDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China (W.H., Z.Y., W.Z., Z.L., Y.M.); Cancer Institute, Fudan University Shanghai Cancer Center; Collaborative Innovation Center of Cancer Medicine; and Department of Oncology, Shanghai Medical College, Shanghai, China (W.H., C.L., L.L., Y.J., G.Y., L.J.); Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China (C.L., Y.J., G.Y., Y.C.); Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China (S.D.); AntiCancer Biotech Beijing Co. Ltd., Beijing, China (M.Y.); Shanghai Shines Clinical Laboratories, Inc., The Research base of MDT, DCMST, Ministry of Health, Shanghai, China (Y.Z.); The Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China (Y.M.).
Chunjie LiDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China (W.H., Z.Y., W.Z., Z.L., Y.M.); Cancer Institute, Fudan University Shanghai Cancer Center; Collaborative Innovation Center of Cancer Medicine; and Department of Oncology, Shanghai Medical College, Shanghai, China (W.H., C.L., L.L., Y.J., G.Y., L.J.); Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China (C.L., Y.J., G.Y., Y.C.); Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China (S.D.); AntiCancer Biotech Beijing Co. Ltd., Beijing, China (M.Y.); Shanghai Shines Clinical Laboratories, Inc., The Research base of MDT, DCMST, Ministry of Health, Shanghai, China (Y.Z.); The Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China (Y.M.).
Zixiao YangDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China (W.H., Z.Y., W.Z., Z.L., Y.M.); Cancer Institute, Fudan University Shanghai Cancer Center; Collaborative Innovation Center of Cancer Medicine; and Department of Oncology, Shanghai Medical College, Shanghai, China (W.H., C.L., L.L., Y.J., G.Y., L.J.); Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China (C.L., Y.J., G.Y., Y.C.); Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China (S.D.); AntiCancer Biotech Beijing Co. Ltd., Beijing, China (M.Y.); Shanghai Shines Clinical Laboratories, Inc., The Research base of MDT, DCMST, Ministry of Health, Shanghai, China (Y.Z.); The Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China (Y.M.).
Lihui LiDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China (W.H., Z.Y., W.Z., Z.L., Y.M.); Cancer Institute, Fudan University Shanghai Cancer Center; Collaborative Innovation Center of Cancer Medicine; and Department of Oncology, Shanghai Medical College, Shanghai, China (W.H., C.L., L.L., Y.J., G.Y., L.J.); Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China (C.L., Y.J., G.Y., Y.C.); Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China (S.D.); AntiCancer Biotech Beijing Co. Ltd., Beijing, China (M.Y.); Shanghai Shines Clinical Laboratories, Inc., The Research base of MDT, DCMST, Ministry of Health, Shanghai, China (Y.Z.); The Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China (Y.M.).
Yanan JiangDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China (W.H., Z.Y., W.Z., Z.L., Y.M.); Cancer Institute, Fudan University Shanghai Cancer Center; Collaborative Innovation Center of Cancer Medicine; and Department of Oncology, Shanghai Medical College, Shanghai, China (W.H., C.L., L.L., Y.J., G.Y., L.J.); Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China (C.L., Y.J., G.Y., Y.C.); Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China (S.D.); AntiCancer Biotech Beijing Co. Ltd., Beijing, China (M.Y.); Shanghai Shines Clinical Laboratories, Inc., The Research base of MDT, DCMST, Ministry of Health, Shanghai, China (Y.Z.); The Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China (Y.M.).
Guangyang YuDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China (W.H., Z.Y., W.Z., Z.L., Y.M.); Cancer Institute, Fudan University Shanghai Cancer Center; Collaborative Innovation Center of Cancer Medicine; and Department of Oncology, Shanghai Medical College, Shanghai, China (W.H., C.L., L.L., Y.J., G.Y., L.J.); Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China (C.L., Y.J., G.Y., Y.C.); Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China (S.D.); AntiCancer Biotech Beijing Co. Ltd., Beijing, China (M.Y.); Shanghai Shines Clinical Laboratories, Inc., The Research base of MDT, DCMST, Ministry of Health, Shanghai, China (Y.Z.); The Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China (Y.M.).
Wei ZhuDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China (W.H., Z.Y., W.Z., Z.L., Y.M.); Cancer Institute, Fudan University Shanghai Cancer Center; Collaborative Innovation Center of Cancer Medicine; and Department of Oncology, Shanghai Medical College, Shanghai, China (W.H., C.L., L.L., Y.J., G.Y., L.J.); Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China (C.L., Y.J., G.Y., Y.C.); Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China (S.D.); AntiCancer Biotech Beijing Co. Ltd., Beijing, China (M.Y.); Shanghai Shines Clinical Laboratories, Inc., The Research base of MDT, DCMST, Ministry of Health, Shanghai, China (Y.Z.); The Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China (Y.M.).
Zhengyan LiuDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China (W.H., Z.Y., W.Z., Z.L., Y.M.); Cancer Institute, Fudan University Shanghai Cancer Center; Collaborative Innovation Center of Cancer Medicine; and Department of Oncology, Shanghai Medical College, Shanghai, China (W.H., C.L., L.L., Y.J., G.Y., L.J.); Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China (C.L., Y.J., G.Y., Y.C.); Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China (S.D.); AntiCancer Biotech Beijing Co. Ltd., Beijing, China (M.Y.); Shanghai Shines Clinical Laboratories, Inc., The Research base of MDT, DCMST, Ministry of Health, Shanghai, China (Y.Z.); The Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China (Y.M.).
Shengzhong DuanDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China (W.H., Z.Y., W.Z., Z.L., Y.M.); Cancer Institute, Fudan University Shanghai Cancer Center; Collaborative Innovation Center of Cancer Medicine; and Department of Oncology, Shanghai Medical College, Shanghai, China (W.H., C.L., L.L., Y.J., G.Y., L.J.); Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China (C.L., Y.J., G.Y., Y.C.); Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China (S.D.); AntiCancer Biotech Beijing Co. Ltd., Beijing, China (M.Y.); Shanghai Shines Clinical Laboratories, Inc., The Research base of MDT, DCMST, Ministry of Health, Shanghai, China (Y.Z.); The Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China (Y.M.).
Yiwei ChuDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China (W.H., Z.Y., W.Z., Z.L., Y.M.); Cancer Institute, Fudan University Shanghai Cancer Center; Collaborative Innovation Center of Cancer Medicine; and Department of Oncology, Shanghai Medical College, Shanghai, China (W.H., C.L., L.L., Y.J., G.Y., L.J.); Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China (C.L., Y.J., G.Y., Y.C.); Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China (S.D.); AntiCancer Biotech Beijing Co. Ltd., Beijing, China (M.Y.); Shanghai Shines Clinical Laboratories, Inc., The Research base of MDT, DCMST, Ministry of Health, Shanghai, China (Y.Z.); The Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China (Y.M.).
Meng YangDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China (W.H., Z.Y., W.Z., Z.L., Y.M.); Cancer Institute, Fudan University Shanghai Cancer Center; Collaborative Innovation Center of Cancer Medicine; and Department of Oncology, Shanghai Medical College, Shanghai, China (W.H., C.L., L.L., Y.J., G.Y., L.J.); Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China (C.L., Y.J., G.Y., Y.C.); Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China (S.D.); AntiCancer Biotech Beijing Co. Ltd., Beijing, China (M.Y.); Shanghai Shines Clinical Laboratories, Inc., The Research base of MDT, DCMST, Ministry of Health, Shanghai, China (Y.Z.); The Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China (Y.M.).
Yanmei ZhangDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China (W.H., Z.Y., W.Z., Z.L., Y.M.); Cancer Institute, Fudan University Shanghai Cancer Center; Collaborative Innovation Center of Cancer Medicine; and Department of Oncology, Shanghai Medical College, Shanghai, China (W.H., C.L., L.L., Y.J., G.Y., L.J.); Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China (C.L., Y.J., G.Y., Y.C.); Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China (S.D.); AntiCancer Biotech Beijing Co. Ltd., Beijing, China (M.Y.); Shanghai Shines Clinical Laboratories, Inc., The Research base of MDT, DCMST, Ministry of Health, Shanghai, China (Y.Z.); The Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China (Y.M.).
Ying MaoDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China (W.H., Z.Y., W.Z., Z.L., Y.M.); Cancer Institute, Fudan University Shanghai Cancer Center; Collaborative Innovation Center of Cancer Medicine; and Department of Oncology, Shanghai Medical College, Shanghai, China (W.H., C.L., L.L., Y.J., G.Y., L.J.); Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China (C.L., Y.J., G.Y., Y.C.); Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China (S.D.); AntiCancer Biotech Beijing Co. Ltd., Beijing, China (M.Y.); Shanghai Shines Clinical Laboratories, Inc., The Research base of MDT, DCMST, Ministry of Health, Shanghai, China (Y.Z.); The Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China (Y.M.).
Lijun JiaDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China (W.H., Z.Y., W.Z., Z.L., Y.M.); Cancer Institute, Fudan University Shanghai Cancer Center; Collaborative Innovation Center of Cancer Medicine; and Department of Oncology, Shanghai Medical College, Shanghai, China (W.H., C.L., L.L., Y.J., G.Y., L.J.); Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China (C.L., Y.J., G.Y., Y.C.); Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China (S.D.); AntiCancer Biotech Beijing Co. Ltd., Beijing, China (M.Y.); Shanghai Shines Clinical Laboratories, Inc., The Research base of MDT, DCMST, Ministry of Health, Shanghai, China (Y.Z.); The Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China (Y.M.).
Fudan University Shanghai Cancer Center · CNShanghai Institutes for Biological Sciences · CNShanghai Medical College of Fudan University · CNSinovac Biotech · CNCancer Institute (WIA) · INChinese Academy of Sciences · CNFudan University · CNShanghai Center for Brain Science and Brain-Inspired Technology · CN
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe neddylation pathway has been recently identified as an attractive anticancer target, and MLN4924, a specific NEDD8-activating enzyme inhibitor, has been developed as a first-in-class anticancer agent. However, neither the status of the neddylation pathway in glioblastoma (GBM) nor the effect of MLN4924 against GBM has been systematically investigated yet.
methodsTo measure the activation state of the neddylation pathway in GBM, expression of the NEDD8-activating enzyme (E1), NEDD8-conjugating enzyme (E2), and global protein neddylation in GBM tumor tissues versus adjacent tissues were examined by immunoblotting analysis and immunohistochemistry staining. To assess the therapeutic efficacy of neddylation inhibition in GBM, cell proliferation in vitro and tumor growth in vivo were determined upon neddylation inhibition by MLN4924, an investigational NEDD8-activating enzyme inhibitor.
resultsThe neddylation pathway was overactivated in a majority of GBM tumor tissues when compared with adjacent normal tissues. The upregulation of this pathway in GBM tissues was positively correlated with high-grade disease and postoperative recurrence but was negatively associated with patient overall survival. MLN4924 treatment inhibited cullin neddylation, inactivated cullin-RING E3 ligase, and led to the accumulation of tumor-suppressive cullin-RING E3 ligase substrates to trigger cell-cycle arrest and senescence or apoptosis in a cell-line dependent manner. Moreover, inhibition of neddylation by MLN4924 significantly suppressed tumor growth in an orthotopic xenograft model of human GBM.
conclusionOur study indicates that an overactivated neddylation pathway may be involved in GBM progression and that inhibition of this oncogenic pathway is a potentially new therapeutic approach for GBM.
Indexed as
Antineoplastic AgentsApoptosisBrain NeoplasmsCell Cycle CheckpointsCell Line, TumorCullin ProteinsCyclopentanesDisease ProgressionGlioblastomaHumansNEDD8 ProteinPyrimidinesSignal TransductionUbiquitinsXenograft Model Antitumor AssaysAntineoplastic AgentsCullin ProteinsCyclopentanesNEDD8 ProteinNEDD8 protein, humanpevonedistatPyrimidinesUbiquitinscullin-RING E3 ligaseglioblastomaMLN4924NEDD8neddylation
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