ArticleSignal transduction and targeted therapy2020
The deubiquitylase UCHL3 maintains cancer stem-like properties by stabilizing the aryl hydrocarbon receptor.
Article in Signal transduction and targeted therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
67 citing papers in PubMed, 85 citations in OpenAlex.
- Aryl hydrocarbon receptor pharmacology-mechanisms, ligands, and therapeutic potential.Pharmacological reviews · 2026Review
- UCHL3 Promotes Triple-Negative Breast Cancer Metastatic Potential Through Enhancing Cell Migration and Invasion.Applied biochemistry and biotechnology · 2026Article
- Targeting UCHL3 attenuates pathological markers in neuronal models of Huntington's disease.Brain : a journal of neurology · 2026Article
- Proline/serine-rich coiled-coil 1 alleviates atherosclerosis via remodeling tryptophan metabolism mediated by Akkermansia muciniphila.Experimental & molecular medicine · 2026Article
- ACTG1 promotes breast cancer aggressiveness and confers ribociclib resistance by deubiquitinating HSPA8 through UCHL3.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- The deubiquitinating enzyme UCHL3 promotes bladder cancer progression and glycolysis through enhancing PKM2 protein stability.Frontiers in oncology · 2026Article
- Mechano-immune interactions in musculoskeletal aging: Mechanisms and translational perspectives.Theranostics · 2026Review
- Reimagining AHR in Cancer: From Environmental Sensor to Novel Immunomodulatory Therapeutic Target.International journal of biological sciences · 2026Review
- Article
- UCHL3 depletion inhibits gastric cancer progression and enhances palbociclib sensitivity by regulating the AKT/CCND1 signaling axis via ENO1 ubiquitination.Cell death & disease · 2025Article
- Ginsenoside Rh2 as a novel PIN1 inhibitor disrupting the cancer stem cell-like phenotype in non-small cell lung cancer.Journal of translational medicine · 2025Article
- UCHL3: a crucial deubiquitinase in DNA damage repair and tumor progression.Cancer cell international · 2025Review
- USP18 deubiquitinates and stabilizes SOX9 to promote the stemness and malignant progression of glioblastoma.Cell death discovery · 2025Article
- Article
- Targeting the JAK2-STAT3-UCHL3-ENO1 axis suppresses glycolysis and enhances the sensitivity to 5-FU chemotherapy inActa pharmaceutica Sinica. B · 2025Article
- NGR-Modified CAF-Derived exos Targeting Tumor Vasculature to Induce Ferroptosis and Overcome Chemoresistance in Osteosarcoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- The role of PM2.5 exposure in lung cancer: mechanisms, genetic factors, and clinical implications.EMBO molecular medicine · 2025Review
- Aryl Hydrocarbon Receptor (AHR) Suppresses Arsenic (AsInternational journal of biological sciences · 2025Article
- Review
7 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer stem cells (CSCs) exhibit highly aggressive and metastatic features and resistance to chemotherapy and radiotherapy. Aryl hydrocarbon receptor (AhR) expression varies among non-small cell lung cancers (NSCLCs), and the mechanisms that support abnormal AhR expression in CSCs remain elusive. Here, we identified ubiquitin carboxyl terminal hydrolase L3 (UCHL3), a DUB enzyme in the UCH protease family, as a bona fide deubiquitylase of the AhR in NSCLC. UCHL3 was shown to interact with, deubiquitylate, and stabilize AhR in a manner dependent on its deubiquitylation activity. Moreover, we showed that UCHL3 promotes the stem-like characteristics and potent tumorigenic capacity of NSCLC cells. UCHL3 increased AhR stability and the binding of AhR to the promoter regions of the "stemness" genes ATP-binding cassette subfamily G member 2 (ABCG2), KLF4, and c-Myc. Depletion of UCHL3 markedly downregulated the "stemness" genes ABCG2, KLF4, and c-Myc, leading to the loss of self-renewal and tumorigenesis in NSCLCs. Furthermore, the UCHL3 inhibitor TCID induced AhR degradation and exhibited significantly attenuated efficacy in NSCLC cells with stem cell-like properties. Additionally, UCHL3 was shown to indicate poor prognosis in patients with lung adenocarcinoma. In general, our results reveal that the UCHL3 deubiquitylase is pivotal for AhR protein stability and a potential target for NSCLC-targeted therapy.
Indexed as
Identifiers
What OpenQuestion holds
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.