ArticleBMC cancer2018
Inhibition of neddylation facilitates cell migration through enhanced phosphorylation of caveolin-1 in PC3 and U373MG cells.
Article in BMC cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Low-Dose MLN4924 Enhances SH-SY5Y Cell Viability and Migration by Targeting SOCS3 Signaling.Doklady. Biochemistry and biophysics · 2025Article
- Ubiquitination Process Mediates Prostate Cancer Development and Metastasis through Multiple Mechanisms.Cell biochemistry and biophysics · 2024Review
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- Molecular mechanisms underlying the promotion of wound repair by coenzyme Q10: PI3K/Akt signal activation via alterations to cell membrane domains.Journal of clinical biochemistry and nutrition · 2022Article
- The Cellular and Developmental Roles of Cullins, Neddylation, and the COP9 Signalosome inFrontiers in physiology · 2022Review
- EPS364, a Novel Deep-Sea Bacterial Exopolysaccharide, Inhibits Liver Cancer Cell Growth and Adhesion.Marine drugs · 2021Article
- The Effect of Neddylation Blockade on Slug-Dependent Cancer Cell Migration Is Regulated by p53 Mutation Status.Cancers · 2021Article
- Neddylation blockade induces HIF-1α driven cancer cell migration via upregulation of ZEB1.Scientific reports · 2020Article
- Review
- Neddylation inactivation represses androgen receptor transcription and inhibits growth, survival and invasion of prostate cancer cells.Neoplasia (New York, N.Y.) · 2020Article
- The importance of caveolins and caveolae to dermatology: Lessons from the caves and beyond.Experimental dermatology · 2020Review
- Inhibition of neddylation causes meiotic arrest in mouse oocyte.Cell cycle (Georgetown, Tex.) · 2019Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundProtein neddylation is a post-translational modification by a covalent conjugation with the neural precursor cell expressed, developmentally downregulated 8 (NEDD8). Although this process has been reported to participate in diverse cellular signaling, little is known about its role in cancer cell migration. Given a recent proteomics report showing that NEDD8 is downregulated in prostate cancer tissues versus normal prostate tissues, we tested the possibility that neddylation plays a role in cancer evolution, and then tried to identify target proteins of the neddylation.
methodsThe neddylation process was inhibited by transfecting cancer cells with NEDD8-targeting siRNAs or by treating the cells with a NAE1 inhibitor MLN4924. Cell migration was evaluated by an in vitro wound-healing assay and a Transwell migration assay. His/NEDD8-conjugated proteins were pulled down with nickel-affinity beads under a denaturing condition, and identified by Western blotting. All data were processed using the Microsoft Excel program and analyzed statistically by two-sided, unpaired Student's t-test.
resultsCaveolin-1, which plays a critical role in cell migration, was identified to be conjugated with NEDD8. When the neddylation was inhibited, the phosphorylation of caveolin-1 at Tyr14 was augmented in PC3 and U373MG cells, thereby leading to increased cell migration. Such consequences by neddylation inhibition were abolished in the presence of a Src family kinase inhibitor PP2.
conclusionsNEDD8 seems to inhibit the Src-mediated phosphorylation of caveolin-1 by modifying the structure of caveolin-1 protein, which blocks the migration of cancer cells. Although the neddylation process is currently regarded as an emerging target for cancer therapy, our results suggest the possibility that the inhibition of neddylation could facilitate cancer invasion or metastasis at least in some types of cancers.
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