ArticleOncogene2018
The E3 ligase C-CBL inhibits cancer cell migration by neddylating the proto-oncogene c-Src.
Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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Who cites it
29 citing papers in PubMed, 41 citations in OpenAlex.
- Neddylation of NFATc1 and Runx2 regulates osteoclast-osteoblast balance and represents a dual-action therapeutic target for postmenopausal osteoporosis.Experimental & molecular medicine · 2026Article
- Decoding neddylation in malignancies: molecular mechanisms, biological functions, therapeutic resistance, and clinical potential.Cell death & disease · 2026Review
- Progression on Mechanism and Therapeutic Implications of Neddylation in Lung Cancer.Oncology research · 2026Review
- Integration analysis of single-cell and spatial transcriptomics identifies prognostic genes associated with neddylation in colorectal cancer.Discover oncology · 2025Article
- Low-Dose MLN4924 Enhances SH-SY5Y Cell Viability and Migration by Targeting SOCS3 Signaling.Doklady. Biochemistry and biophysics · 2025Article
- The E3 ubiquitin ligase TRIM56 promotes aggregation and activation of Src protein through Lys63-linked polyubiquitination in hepatocellular carcinoma.Cell death & disease · 2025Article
- The Double-Edged Effects of MLN4924: Rethinking Anti-Cancer Drugs Targeting the Neddylation Pathway.Biomolecules · 2024Review
- Article
- Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024Review
- Neddylation of insulin receptor substrate acts as a bona fide regulator of insulin signaling and its implications for cancer cell migration.Cancer gene therapy · 2024Article
- Neddylation of protein, a new strategy of protein post-translational modification for targeted treatment of central nervous system diseases.Frontiers in neuroscience · 2024Review
- The role of CBL family ubiquitin ligases in cancer progression and therapeutic strategies.Frontiers in pharmacology · 2024Review
- Discovery of neddylation E2s inhibitors with therapeutic activity.Oncogenesis · 2023Review
- An inventory of crosstalk between ubiquitination and other post-translational modifications in orchestrating cellular processes.iScience · 2023Review
- Targeting neddylation as a novel approach to lung cancer treatment (Review).International journal of oncology · 2023Review
- Neddylation of EphB1 Regulates Its Activity and Associates with Liver Fibrosis.International journal of molecular sciences · 2023Article
- Hepatic neddylation deficiency triggers fatal liver injury via inducing NF-κB-inducing kinase in mice.Nature communications · 2022Article
- UM-164, a Dual Inhibitor of c-Src and p38 MAPK, Suppresses Proliferation of Glioma by Reducing YAP Activity.Cancers · 2022Article
- Neddylation pattern indicates tumor microenvironment characterization and predicts prognosis in lung adenocarcinoma.Frontiers in cell and developmental biology · 2022Article
- The Role of Membrane-Associated E3 Ubiquitin Ligases in Cancer.Frontiers in pharmacology · 2022Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
Neddylation is a cellular process that covalently conjugates substrate proteins with the small ubiquitin-like molecule NEDD8. As neddylation is required for fast turnover of proteins in proliferating cancer cells, the neddylation process is currently regarded as a potential target for cancer therapy. However, little is known about the role of neddylation in cancer invasion and metastasis. Unexpectedly, we here found that the neddylation blockade stimulates migration of lung cancer and glioblastoma cells. Mechanistically, C-CBL acts as the E3 ligase for neddylation of the proto-oncogene c-Src. After neddylation, c-Src is poly-ubiquitinated and degraded through the proteasome, which inhibits the PI3K-AKT pathway responsible for cell migration. In human lung cancer tissues, the downregulation of C-CBL was associated with c-Src/AKT, cancer metastasis, and poor survival in patients. Therefore, C-CBL is likely to play a tumor suppressive role by antagonizing a robust oncogenic signaling driven by c-Src. This study provides new insight about the role of neddylation in cancer metastasis. It also implies that the metastasis risk should be carefully evaluated before the clinical application of neddylation inhibitors as anticancer regimens.
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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 Socratic graph.