ArticleInternational journal of molecular sciences2019
Inhibition of UCH-L1 Deubiquitinating Activity with Two Forms of LDN-57444 Has Anti-Invasive Effects in Metastatic Carcinoma Cells.
Article in International journal of molecular sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Extracellular Vesicles in Oral Squamous Cell Carcinoma and Oral Potentially Malignant Disorders: A Systematic Review.International journal of molecular sciences · 2020Pooled it
- Tied to Work: Topologically Knotted SPOUT Methyltransferases and UCH Deubiquitinases in Cellular Biochemistry.Journal of cellular biochemistry · 2026Review
- UCHL1 Promotes Gastric Cancer Progression by Regulating CIP2A Degradation.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Evolving role of deubiquitinating enzymes in oral cancer (Review).Oncology letters · 2025Review
- Effect of deubiquitinases in head and neck squamous cell carcinoma (Review).Oncology letters · 2025Review
- Broad-spectrum ubiquitin-specific protease inhibition as a mechanism for the cytotoxicity of YM155 in cancers.Scientific reports · 2025Article
- Article
- Emerging roles of deubiquitinating enzymes in actin cytoskeleton and tumor metastasis.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- Review
- Ubiquitin C‑terminal hydrolase‑L1: A new cancer marker and therapeutic target with dual effects (Review).Oncology letters · 2023Review
- Pivotal Role of Ubiquitin Carboxyl-Terminal Hydrolase L1 (UCHL1) in Uterine Leiomyoma.Biomolecules · 2023Article
- Extracellular Vesicles and Fatty Liver.Advances in experimental medicine and biology · 2023Review
- Exosome biogenesis: machinery, regulation, and therapeutic implications in cancer.Molecular cancer · 2022Review
- UCHL1 acts as a potential oncogene and affects sensitivity of common anti-tumor drugs in lung adenocarcinoma.World journal of surgical oncology · 2022Article
- Review
- UCHL1 as a novel target in breast cancer: emerging insights from cell and chemical biology.British journal of cancer · 2022Review
- Targeting the Ubiquitin-Proteasome System for Cancer Therapeutics by Small-Molecule Inhibitors.Cancers · 2021Review
- Poly(2-oxazoline)- and Poly(2-oxazine)-Based Self-Assemblies, Polyplexes, and Drug Nanoformulations-An Update.Advanced healthcare materials · 2021Review
- The roles of extracellular vesicles in the development, microenvironment, anticancer drug resistance, and therapy of head and neck squamous cell carcinoma.Journal of experimental & clinical cancer research : CR · 2021Review
- The role of Exosomes in the Pathogenesis of Nasopharyngeal Carcinoma and the involved Clinical Application.International journal of biological sciences · 2021Review
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Authors and funding
11 authors at 2 institutions in 3 countries.
Funding
Abstract
Normally ubiquitin C-terminal hydrolase L1 (UCH-L1) is expressed in the central nervous and reproductive systems of adults, but its de novo expression has been detected in many human cancers. There is a growing body of evidence that UCH-L1 de-ubiquitinating (DUB) activity plays a major pro-metastatic role in certain carcinomas. Here we tested anti-metastatic effects of the small-molecule inhibitor of UCH-L1 DUB activity, LDN-57444, in cell lines from advanced oral squamous cell carcinoma (OSCC) as well as invasive nasopharyngeal (NP) cell lines expressing the major pro-metastatic gene product of Epstein-Barr virus (EBV) tumor virus, LMP1. To overcome the limited aqueous solubility of LDN-57444 we developed a nanoparticle formulation of LDN-57444 by incorporation of the compound in polyoxazoline micellear nanoparticles (LDN-POx). LDN-POx nanoparticles were equal in effects as the native compound in vitro. Our results demonstrate that inhibition of UCH-L1 DUB activity with LDN or LDN-POx inhibits secretion of exosomes and reduces levels of the pro-metastatic factor in exosomal fractions. Both forms of UCH-L1 DUB inhibitor suppress motility of metastatic squamous carcinoma cells as well as nasopharyngeal cells expressing EBV pro-metastatic Latent membrane protein 1 (LMP1) in physiological assays. Moreover, treatment with LDN and LDN-POx resulted in reduced levels of pro-metastatic markers, a decrease of carcinoma cell adhesion, as well as inhibition of extra-cellular vesicle (ECV)-mediated transfer of viral invasive factor LMP1. We suggest that soluble inhibitors of UCH-L1 such as LDN-POx offer potential forms of treatment for invasive carcinomas including EBV-positive malignancies.
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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 OpenQuestion graph.