ArticleScientific reports2016
Neddylation inhibitor MLN4924 suppresses growth and migration of human gastric cancer cells.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 111 citations in OpenAlex.
- A Phase I study of pevonedistat plus capecitabine plus oxaliplatin in patients with advanced gastric cancer refractory to platinum (NCCH-1811).Future science OA · 2021Trial
- Neddylation: from regulatory mechanisms to clinical implications in cancer.Journal of advanced research · 2026Review
- SLC25A11-mediated reprogramming of mitochondrial redox state and lipid peroxidation confers NRF2-dependent ferroptosis resistance in biliary tract cancer.Cellular & molecular biology letters · 2026Article
- Stage-Specific Regulation of Ubiquitination Modifications and Prospects for Targeted Therapy in Triple-Negative Breast Cancer.Oncology research · 2026Review
- Phase I study of pevonedistat combined with capecitabine and oxaliplatin in patients with platinum-refractory advanced gastric cancer.Scientific reports · 2025Article
- Construction and validation of a post-translational modification-related signature to predict the effect of immune therapies in gastric cancer.Biochemistry and biophysics reports · 2025Article
- Inhibiting neddylation: A new strategy for tumor therapy.Journal of pharmaceutical analysis · 2025Review
- YTHDF1/RNF7/p27 axis promotes prostate cancer progression.Cell death & disease · 2025Article
- Targeting HBV cccDNA Levels: Key to Achieving Complete Cure of Chronic Hepatitis B.Pathogens (Basel, Switzerland) · 2024Review
- An Anti-Invasive Role for Mdmx through the RhoA GTPase under the Control of the NEDD8 Pathway.Cells · 2024Article
- Epigenetic modulation through BET bromodomain inhibitors as a novel therapeutic strategy for progranulin-deficient frontotemporal dementia.Scientific reports · 2024Article
- Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024Review
- Advancements in colorectal cancer research: Unveiling the cellular and molecular mechanisms of neddylation (Review).International journal of oncology · 2024Review
- Optical Control of Proteasomal Protein Degradation with a Photoswitchable Lipopeptide.Angewandte Chemie (International ed. in English) · 2024Article
- Article
- Role of non-canonical post-translational modifications in gastrointestinal tumors.Cancer cell international · 2023Review
- BRWD3 promotes KDM5 degradation to maintain H3K4 methylation levels.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Targeting NEDD8-activating enzyme for cancer therapy: developments, clinical trials, challenges and future research directions.Journal of hematology & oncology · 2023Review
- NEDD8-Activating Enzyme Inhibitor MLN4924 Inhibits Both the Tumor Stroma and Angiogenesis in Pancreatic Cancer via Gli1 and REDD1.Digestive diseases and sciences · 2023Article
- BRWD3 promotes KDM5 degradation to maintain H3K4 methylation levels.bioRxiv : the preprint server for biology · 2023Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 2 countries.
Funding
Abstract
MLN4924 is a recently discovered small molecule inhibitor of NEDD8-Activating Enzyme (NAE). Because cullin RING ligase (CRL), the largest family of E3 ubiquitin ligase, requires cullin neddylation for its activity, MLN4924, therefore, acts as an indirect inhibitor of CRL by blocking cullin neddylation. Given that CRLs components are up-regulated, whereas neddylation modification is over-activated in a number of human cancers, MLN4924 was found to be effective in growth suppression of cancer cells. Whether MLN4924 is effective against gastric cancer cells, however, remains elusive. Here we showed that in gastric cancer cells, MLN4924 rapidly inhibited cullin 1 neddylation and remarkably suppressed growth and survival as well as migration in a dose-and time-dependent manner. Mechanistic studies in combination with siRNA knockdown-based rescue experiments revealed that MLN4924 induced the accumulation of a number of CRL substrates, including CDT1/ORC1, p21/p27, and PHLPP1 to trigger DNA damage response and induce growth arrest at the G2/M phase, to induce senescence, as well as autophagy, respectively. MLN4924 also significantly suppressed migration by transcriptionally activating E-cadherin and repressing MMP-9. Taken together, our study suggest that neddylation modification and CRL E3 ligase are attractive gastric cancer targets, and MLN4924 might be further developed as a potent therapeutic agent for the treatment of gastric cancer.
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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.