ArticleAmerican journal of cancer research2020
Neddylation inhibitor, MLN4924 suppresses angiogenesis in huvecs and solid cancers:
Article in American journal of cancer research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 26 citations in OpenAlex.
- Endothelial deletion of the neddylation E2 enzyme UBE2M inhibits tumor growth by promoting nonproductive angiogenesis.The Journal of clinical investigation · 2026Article
- Neddylation: from regulatory mechanisms to clinical implications in cancer.Journal of advanced research · 2026Review
- Integration analysis of single-cell and spatial transcriptomics identifies prognostic genes associated with neddylation in colorectal cancer.Discover oncology · 2025Article
- Neddylation related gene signature for prognostic biomarkers in colorectal cancer with integrated bioinformatics and experimental analysis.Discover oncology · 2025Article
- Acid-catalysed rearrangement of acyl groups: synthesis of β-d-gluco aminocyclopentitols and carbanucleoside derivatives.RSC advances · 2025Article
- NEDDylation Regulates CD8+ T-cell Metabolism and Antitumor Immunity.Cancer immunology research · 2025Article
- Promising Therapeutic Strategies for Hematologic Malignancies: Innovations and Potential.Molecules (Basel, Switzerland) · 2024Review
- The Double-Edged Effects of MLN4924: Rethinking Anti-Cancer Drugs Targeting the Neddylation Pathway.Biomolecules · 2024Review
- Advancements in colorectal cancer research: Unveiling the cellular and molecular mechanisms of neddylation (Review).International journal of oncology · 2024Review
- Review
- Article
- Deciphering the role of neddylation in tumor microenvironment modulation: common outcome of multiple signaling pathways.Biomarker research · 2024Review
- NEDD8-Activating Enzyme Inhibitor MLN4924 Inhibits Both the Tumor Stroma and Angiogenesis in Pancreatic Cancer via Gli1 and REDD1.Digestive diseases and sciences · 2023Article
- Targeting cullin neddylation for cancer and fibrotic diseases.Theranostics · 2023Review
- CpG-binding protein CFP1 promotes ovarian cancer cell proliferation by regulating BST2 transcription.Cancer gene therapy · 2022Article
- The roles of histone modifications in tumorigenesis and associated inhibitors in cancer therapy.Journal of the National Cancer Center · 2022Review
- Inhibition of NEDD8 NEDDylation induced apoptosis in acute myeloid leukemia cells via p53 signaling pathway.Bioscience reports · 2022Article
- Cdk2 suppresses IL-23 expression and the onset of severe acute pancreatitis.Immunity, inflammation and disease · 2022Article
- A review on cullin neddylation and strategies to identify its inhibitors for cancer therapy.3 Biotech · 2022Article
- AHRR contributes to inflammatory lymphangiogenesis by activating the EPAS1/VEGFD signaling axis in head and neck cancer.American journal of cancer research · 2022Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cullin-RING E3 ligases are involved in the ubiquitination of substrates that regulate important biological processes and are a potential therapeutic target in many types of cancer. MLN4924, a small molecule of NEDD8-activating enzyme inhibitor, inactivates CRL by blocking cullin neddylation and has been reported to elicit anti-tumor effect. In this study, In this study, we aimed to investigate the effects of MLN4924 on angiogenesis in human umbilical vascular endothelial cells (HUVECs) and four types of cancer cells. Our results showed that MLN4924 inhibits cell viability and induced apoptosis in HUVECs in a dose-dependent manner. MLN4924 inhibits proliferation and interferes with the cell cycle checkpoint regulators, p21, p27, and phospho-histone H3. Vascular endothelial growth factor (VEGF) treatment increased the level of UBC12 in HUVECs, indicating that neddylation pathway is involved in VEGF-activated angiogenesis. MLN4924 decreased VEGF-activated cell proliferation via neddylation inhibition. MLN4924 inhibited VEGF-activated cell migration, capillary tube formation and VEGF-mediated Erk1/2 activation in HUVECs. We also examined antitumor effect of MLN4924 using xenograft SCID mouse models of four different types of cancer cells. The in vivo results showed MLN4924 inhibited tumor growth in all four types of cancers with decreasing CD31 expression in xenograft tumor. In conclusion, MLN4924 inhibited viability, migration, and VEGF-promoted angiogenic activity in HUVECs; consistently, MLN4924 inhibited tumor growth in four types of cancers with suppression of angiogenesis. These findings provide evidence to develop therapeutic strategy for cancer treatment through anti-angiogenesis through neddylation inhibition.
Indexed as
Identifiers
32266102PMC7136913W3014675377What OpenQuestion holds
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.