ArticleCell proliferation2019
The Nedd8-activating enzyme inhibitor MLN4924 (TAK-924/Pevonedistat) induces apoptosis via c-Myc-Noxa axis in head and neck squamous cell carcinoma.
Article in Cell proliferation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Autophagy and ubiquitination in important swine viral infections: Host defense and viral antagonism.Virulence · 2026Review
- MLN4924 suppresses kidney renal clear cell carcinoma progression through coordinated inhibition of Cullin1 neddylation and PSMB10-associated NF-κB inflammatory signaling.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Unbiased CRISPR synthetic lethal screening for genetic vulnerabilities in a succinate dehydrogenase-loss model of paraganglioma.iScience · 2026Article
- Decoding neddylation in malignancies: molecular mechanisms, biological functions, therapeutic resistance, and clinical potential.Cell death & disease · 2026Review
- The Double-Edged Effects of MLN4924: Rethinking Anti-Cancer Drugs Targeting the Neddylation Pathway.Biomolecules · 2024Review
- Article
- Deciphering the role of neddylation in tumor microenvironment modulation: common outcome of multiple signaling pathways.Biomarker research · 2024Review
- Targeting NEDD8-activating enzyme for cancer therapy: developments, clinical trials, challenges and future research directions.Journal of hematology & oncology · 2023Review
- NEDD8 promotes radioresistance via triggering autophagy formation and serves as a novel prognostic marker in oral squamous cell carcinoma.Cancer cell international · 2023Article
- Targeting cullin neddylation for cancer and fibrotic diseases.Theranostics · 2023Review
- Targeted CUL4A inhibition synergizes with cisplatin to yield long-term survival in models of head and neck squamous cell carcinoma through a DDB2-mediated mechanism.Cell death & disease · 2022Article
- Targeting NEDDylation as a Novel Approach to Improve the Treatment of Head and Neck Cancer.Cancers · 2021Review
- Andrographolide Induces Noxa-Dependent Apoptosis by Transactivating ATF4 in Human Lung Adenocarcinoma Cells.Frontiers in pharmacology · 2021Article
- Regulation of NFκB Signalling by Ubiquitination: A Potential Therapeutic Target in Head and Neck Squamous Cell Carcinoma?Cancers · 2020Review
- Abnormal Cullin1 neddylation-mediated p21 accumulation participates in the pathogenesis of recurrent spontaneous abortion by regulating trophoblast cell proliferation and differentiation.Molecular human reproduction · 2020Article
- Neddylation inhibition activates the protective autophagy through NF-κB-catalase-ATF3 Axis in human esophageal cancer cells.Cell communication and signaling : CCS · 2020Article
- Construction of a water-soluble and photostable rubropunctatin/β-cyclodextrin drug carrier.RSC advances · 2019Article
- The Selection of NFκB Inhibitors to Block Inflammation and Induce Sensitisation to FasL-Induced Apoptosis in HNSCC Cell Lines Is Critical for Their Use as a Prospective Cancer Therapy.International journal of molecular sciences · 2019Article
- The Nedd8-activating enzyme inhibitor MLN4924 (TAK-924/Pevonedistat) induces apoptosis via c-Myc-Noxa axis in head and neck squamous cell carcinoma.Cell proliferation · 2019Article
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Authors and funding
17 authors.
Funding
Abstract
objectivesThe present study aimed to reveal expression status of the neddylation enzymes in HNSCC and to elucidate the anticancer efficacy and the underlying mechanisms of inhibiting neddylation pathway. MATERIALS AND
methodsThe expression levels of neddylation enzymes were estimated by Western blotting in human HNSCC specimens and bioinformatics analysis of the cancer genome atlas (TCGA) database. Cell apoptosis was evaluated by Annexin V fluorescein isothiocyanate/propidium iodide (Annexin V-FITC/PI) stain and fluorescence-activated cell sorting (FACS). Small interfering RNA (siRNA) and the CRISPR-Cas9 system were used to elucidate the underlying molecular mechanism of MLN4924-induced HNSCC apoptosis.
resultsExpression levels of NAE1 and UBC12 were prominently higher in HNSCC tissues than that in normal tissues. Inactivation of the neddylation pathway significantly inhibited malignant phenotypes of HNSCC cells. Mechanistic studies revealed that MLN4924 induced the accumulation of CRL ligase substrate c-Myc that transcriptionally activated pro-apoptotic protein Noxa, which triggered apoptosis in HNSCC.
conclusionsThese findings determined the over-expression levels of neddylation enzymes in HNSCC and revealed novel mechanisms underlying neddylation inhibition induced growth suppression in HNSCC cells, which provided preclinical evidence for further clinical evaluation of neddylation inhibitors (eg, MLN4924) for the treatment of HNSCC.
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