ArticleJournal of cellular and molecular medicine2020
Deubiquitinase inhibitor degrasyn suppresses metastasis by targeting USP5-WT1-E-cadherin signalling pathway in pancreatic ductal adenocarcinoma.
Article in Journal of cellular and molecular medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 33 citations in OpenAlex.
- Stabilization of FASN by USP5-mediated deubiquitination promotes hepatocellular carcinoma progression.Oncogenesis · 2025Article
- The multifaceted roles of deubiquitinating enzymes (DUBs) in pancreatic ductal adenocarcinoma.Cell death & disease · 2025Review
- Unbiased high-throughput screening of drug-repurposing libraries identifies small-molecule inhibitors of clot retraction.Blood advances · 2025Article
- USP5 promotes tumor progression by stabilizing SLUG in bladder cancer.Oncology letters · 2024Article
- Emerging roles of deubiquitinating enzymes in actin cytoskeleton and tumor metastasis.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- Unraveling the Immune Regulatory Functions of USP5: Implications for Disease Therapy.Biomolecules · 2024Review
- Unraveling the Mechanism of Action of Ubiquitin-Specific Protease 5 and Its Inhibitors in Tumors.Clinical Medicine Insights. Oncology · 2024Review
- A pan-cancer analysis of the role of USP5 in human cancers.Scientific reports · 2023Article
- Ubiquitin-Specific Proteases as Potential Therapeutic Targets in Bladder Cancer-In Vitro Evaluation of Degrasyn and PR-619 Activity Using Human and Canine Models.Biomedicines · 2023Article
- Ubiquitin signaling in pancreatic ductal adenocarcinoma.Frontiers in molecular biosciences · 2023Review
- A review of deubiquitinases and thier roles in tumorigenesis and development.Frontiers in bioengineering and biotechnology · 2023Review
- [WP1130 relieves septic shock in mice by inhibiting NLRP3 inflammasome activation].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2022Article
- Review
- WT1: The Hinge Between Anemia Correction and Cancer Development in Chronic Kidney Disease.Frontiers in cell and developmental biology · 2022Review
- Downregulation of microRNA-519 enhances development of lung cancer by mediating the E2F2/PI3K/AKT axis.International journal of clinical and experimental pathology · 2020Article
- Deubiquitinating Enzyme: A Potential Secondary Checkpoint of Cancer Immunity.Frontiers in oncology · 2020Review
- Deubiquitinase inhibitor degrasyn suppresses metastasis by targeting USP5-WT1-E-cadherin signalling pathway in pancreatic ductal adenocarcinoma.Journal of cellular and molecular medicine · 2020Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Wilm's tumour-1 (WT1) is overexpressed in pancreatic ductal adenocarcinoma (PDAC) and enhances metastasis. Deubiquitination stabilizes target proteins, and inhibiting deubiquitination facilitates the degradation of target proteins. However, whether inhibiting deubiquitination of WT1 facilitates its degradation and presents anti-cancer ability in PDAC is unknown. Here, we found that deubiquitinase inhibitor degrasyn rapidly induced the degradation of endogenous and exogenous WT1 through enhancing ubiquitination of WT1 followed by the up-regulation of E-cadherin. Knockdown of WT1 by short hairpin RNAs (shRNAs) inhibited metastasis and overexpression of WT1 partially prevented degrasyn-induced anti-metastasis activity, suggesting that degrasyn presents anti-metastasis activity partially through degrading WT1 protein. We further identified that USP5 deubiquitinated WT1 and stabilized its expression. The higher expressions of USP5 and WT1 are associated with tumour metastasis. More importantly, degrasyn inhibited the activity of USP5 and overexpression of USP5 partially prevented degrasyn-induced degradation of WT1 protein, suggesting that degrasyn degraded WT1 protein through inhibiting the activity of USP5. Finally, degrasyn reduced the tumorigenicity in a xenograft mouse model and reduced the metastasis in vivo. Our results indicate that degrasyn presents strong anti-cancer activity through USP5-WT1-E-cadherin signalling in PDAC. Therefore, degrasyn holds promise as cancer therapeutic agent in PDAC with high expressions of USP5 and WT1.
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