ArticlePloS one2017
Ubiquitin carboxyl-terminal esterase L1 (UCHL1) is associated with stem-like cancer cell functions in pediatric high-grade glioma.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 35 citations in OpenAlex.
- UCHL1 promotes temozolomide resistance in glioblastoma by inhibiting the ubiquitination-mediated degradation of keratin 8.Translational oncology · 2026Article
- Potential Anti-Cancer Drug 6RK73 Suppresses Ovarian Cancer Growth by Inactivating the AKT1/Sp1 Induced c-Myc Signaling Pathway.Journal of Cancer · 2026Article
- Article
- Human anaerobic microbiome: a promising and innovative tool in cancer prevention and treatment by targeting pyruvate metabolism.Cancer immunology, immunotherapy : CII · 2023Review
- MMP-1, UCH-L1, and 20S Proteasome as Potential Biomarkers Supporting the Diagnosis of Brain Glioma.Biomolecules · 2022Article
- Optimization and Anti-Cancer Properties of Fluoromethylketones as Covalent Inhibitors for Ubiquitin C-Terminal Hydrolase L1.Molecules (Basel, Switzerland) · 2021Article
- Transcriptomic Analysis of Diffuse Intrinsic Pontine Glioma (DIPG) Identifies a Targetable ALDH-Positive Subset of Highly Tumorigenic Cancer Stem-like Cells.Molecular cancer research : MCR · 2021Article
- Molecular Mechanisms of DUBs Regulation in Signaling and Disease.International journal of molecular sciences · 2021Review
- The Deubiquitinating Enzyme UCHL1 Induces Resistance to Doxorubicin in HER2+ Breast Cancer by Promoting Free Fatty Acid Synthesis.Frontiers in oncology · 2021Article
- UCH-L1 and UCH-L3 regulate the cancer stem cell-like properties through PI3 K/Akt signaling pathway in prostate cancer cells.Animal cells and systems · 2021Article
- TargetingPathology oncology research : POR · 2021Article
- Ubiquitin C-Terminal Hydrolase L1: Biochemical and Cellular Characterization of a Covalent Cyanopyrrolidine-Based Inhibitor.Chembiochem : a European journal of chemical biology · 2020Article
- Ubiquitin Carboxyl-Terminal Hydrolases and Human Malignancies: The Novel Prognostic and Therapeutic Implications for Head and Neck Cancer.Frontiers in oncology · 2020Review
- Bidirectional Relation Between Parkinson's Disease and Glioblastoma Multiforme.Frontiers in neurology · 2020Review
- The Autophagy Status of Cancer Stem Cells in Gliobastoma Multiforme: From Cancer Promotion to Therapeutic Strategies.International journal of molecular sciences · 2019Review
- Emerging role of F-box proteins in the regulation of epithelial-mesenchymal transition and stem cells in human cancers.Stem cell research & therapy · 2019Review
- Investigating the Protein Signature of Adamantinomatous Craniopharyngioma Pediatric Brain Tumor Tissue: Towards the Comprehension of Its Aggressive Behavior.Disease markers · 2019Article
- Nrf2 inhibition affects cell cycle progression during early mouse embryo development.The Journal of reproduction and development · 2018Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pediatric high-grade gliomas represent 8-12% of all primary tumors of the nervous system in children. Five-year survival for these pediatric aggressive tumors is poor (15-35%) indicating the need to develop better treatments for pediatric high-grade gliomas. In this work we used SF188 and SJ-GBM2 cell lines to study the function of the ubiquitin carboxyl-terminal esterase L1 (UCHL1), a deubiquitinase de-regulated in several cancers, in pediatric high-grade gliomas. UCHL1 depletion in SF188 and SJ-GBM2 glioma cells was associated with decreased cell proliferation and invasion, along with a reduced ability to grow in soft agar and to form spheres (i.e. self-renewal measure). A 70% reduction in Wnt signaling was also observed in the SF188 and SJ-GBM2 UCHL1 knockdowns (KDs) using a TCF-dependent TOPflash reporter assay. Transcriptome comparisons of UCHL1 KDs versus vector control identified a list of 306 differentially expressed genes (at least 2-fold change; p <0.05) which included genes known to be involved in cancer like ACTA2, POSTN, LIF, FBXL7, FBXW11, GDF15, HEY2, but also potential novel genes such us IGLL5, ABCA4, AQP3, AQP4, CALB1, and ALK. Bioinformatics gene ontology (GO) analysis of these 306 genes revealed significant enrichment in "signal peptides", "extracellular matrix"and "secreted proteins" GO Terms. "Angiogenesis and blood vessel development", "neuron differentiation/development", cell adhesion", and "cell migration" also showed significant enrichment in our GO analysis. Top canonical pathways identified by Ingenuity Pathway Analysis (IPA) included "Clathrin-mediated Endocytosis Signaling" (p = 5.14x10-4), "Virus Entry via Endocytic Pathways" (p = 6.15x 10-4), and "High Mobility Group-Box 1 (HMGB1) Signaling" (p = 6.15x10-4). While FGF2, IL1B, TNF and PDGFB were predicted as top upstream regulators (p < 2x10-16) of the UCHL1 KD-associated transcriptome. Aberrant expression of UCHL1 in pediatric high-grade gliomas may promote cell invasion, transformation, and self-renewal properties, at least in part, by modulating Wnt/Beta catenin activity. UCHL1 might act as an oncogene in glioma within the gene network that imparts stem-like characteristics to these cancer cells.
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