ArticleCancers2021
The Effect of Neddylation Blockade on Slug-Dependent Cancer Cell Migration Is Regulated by p53 Mutation Status.
Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- Decoding neddylation in malignancies: molecular mechanisms, biological functions, therapeutic resistance, and clinical potential.Cell death & disease · 2026Review
- Senescence-associated secretory phenotype in lung cancer: remodeling the tumor microenvironment for metastasis and immune suppression.Frontiers in oncology · 2025Review
- Promising Proteolysis-Targeting Chimera for Mutant p53-R175H.ACS omega · 2024Article
- Two-polarized roles of transcription factor FOSB in lung cancer progression and prognosis: dependent on p53 status.Journal of experimental & clinical cancer research : CR · 2024Article
- Neddylation inhibition prevents acetaminophen-induced liver damage by enhancing the anabolic cardiolipin pathway.Cell reports. Medicine · 2024Article
- 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
- Targeting neddylation as a novel approach to lung cancer treatment (Review).International journal of oncology · 2023Review
- Opposing Roles of Wild-type and Mutant p53 in the Process of Epithelial to Mesenchymal Transition.Frontiers in molecular biosciences · 2022Review
- The Cellular and Developmental Roles of Cullins, Neddylation, and the COP9 Signalosome inFrontiers in physiology · 2022Review
- SUMOylation and NEDDylation in Primary and Metastatic Cancers to Bone.Frontiers in cell and developmental biology · 2022Review
- Identification of uterine leiomyosarcoma-associated hub genes and immune cell infiltration pattern using weighted co-expression network analysis and CIBERSORT algorithm.World journal of surgical oncology · 2021Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
The tumor suppressor protein p53 is frequently inactivated in human malignancies, in which it is associated with cancer aggressiveness and metastasis. Because p53 is heavily involved in epithelial-mesenchymal transition (EMT), a primary step in cell migration, p53 regulation is important for preventing cancer metastasis. p53 function can be modulated by diverse post-translational modifications including neddylation, a reversible process that conjugates NEDD8 to target proteins and inhibits the transcriptional activity of p53. However, the role of p53 in cancer migration by neddylation has not been fully elucidated. In this study, we reported that neddylation blockade induces cell migration depending on p53 status, specifically via the EMT-promoting transcription factor Slug. In cancer cell lines expressing wild type p53, neddylation blockade increased the transcriptional activity of p53 and expression of its downstream genes p21 and MDM2, eventually promoting proteasomal degradation of Slug. In the absence of p53, neddylation blockade increased cell migration by activating the PI3K/Akt/mTOR/Slug signaling axis. Because mutant p53 was transcriptionally inactivated but maintained the ability to bind to Slug, neddylation blockade did not affect the migration of cells expressing mutant p53. Our findings highlight how the p53 expression status influences neddylation-mediated cell migration in multiple cancer cell lines via Slug.
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Registered trials
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