ArticleBritish journal of cancer2020
CSN6-TRIM21 axis instigates cancer stemness during tumorigenesis.
Article in British journal of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 34 citations in OpenAlex.
- CSN6 Promotes Pancreatic Cancer Progression and Gemcitabine Resistance via Antagonizing DCAF1-Mediated Ubiquitination of NPM1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- TRIM21 functions as an oncogene in glioblastoma by transactivating FOSL1 and promoting the ubiquitination of p27.Cell communication and signaling : CCS · 2025Article
- Key roles of ubiquitination in regulating critical regulators of cancer stem cell functionality.Genes & diseases · 2025Review
- TRIM21-mediated PRMT1 degradation attenuates colorectal cancer malignant progression.Cell death & disease · 2025Article
- microRNA-2117 Negatively Regulates Liver Cancer Stem Cells Expansion and Chemoresistance Via Targeting SOX2.Molecular carcinogenesis · 2025Article
- EGF-Upregulated lncRNA ESSENCE Promotes Colorectal Cancer Growth through Stabilizing CAD and Ferroptosis Defense.Research (Washington, D.C.) · 2025Article
- The feedback loop between MTA1 and MTA3/TRIM21 modulates stemness of breast cancer in response to estrogen.Cell death & disease · 2024Article
- Diverse roles of aldolase enzymes in cancer development, drug resistance and therapeutic approaches as moonlighting enzymes.Medical oncology (Northwood, London, England) · 2024Review
- Review
- CSN6-SPOP-HMGCS1 Axis Promotes Hepatocellular Carcinoma Progression via YAP1 Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- The EIF3H-HAX1 axis increases RAF-MEK-ERK signaling activity to promote colorectal cancer progression.Nature communications · 2024Article
- Friend or foe? Reciprocal regulation between E3 ubiquitin ligases and deubiquitinases.Biochemical Society transactions · 2024Review
- Human patient derived organoids: an emerging precision medicine model for gastrointestinal cancer research.Frontiers in cell and developmental biology · 2024Review
- The involvement of E3 ubiquitin ligases in the development and progression of colorectal cancer.Cell death discovery · 2023Review
- Article
- Intricate confrontation: Research progress and application potential of TRIM family proteins in tumor immune escape.Journal of advanced research · 2023Review
- TRIM21 enhances bortezomib sensitivity in multiple myeloma by halting prosurvival autophagy.Blood advances · 2023Article
- COPS6 promotes tumor progression and reduces CD8Acta pharmacologica Sinica · 2023Article
- Protein Posttranslational Modification in Stemness Remodeling and Its Emerging Role as a Novel Therapeutic Target in Gastrointestinal Cancers.International journal of molecular sciences · 2023Review
- FBXW7β loss-of-function enhances FASN-mediated lipogenesis and promotes colorectal cancer growth.Signal transduction and targeted therapy · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundCancer stem cells (CSCs) are responsible for tumour initiation, metastasis and recurrence. However, the mechanism of CSC formation, maintenance and expansion in colorectal cancer (CRC) remains poorly characterised.
methodsThe role of COP9 signalosome subunit 6 (CSN6) in regulating cancer stemness was evaluated by organoid formation and limited dilution analysis. The role of CSN6-TRIM21-OCT1-ALDH1A1 axis in CSC formation was evaluated in vitro and in vivo. The association of CSN6, TRIM21 and ALDH1A1 expression was validated by a tissue microarray with 267 CRC patients.
resultsThe results showed that CSN6 is critical for sphere formation and maintaining the growth of patient-derived organoids (PDOs). We characterised the role of CSN6 in regulating cancer stemness, which involves the TRIM21 E3 ubiquitin ligase, transcription factor POU class 2 homeobox 1 (OCT1) and cancer stem cell marker aldehyde dehydrogenase 1 A1 (ALDH1A1). Our data showed that CSN6 facilitates ubiquitin-mediated degradation of TRIM21, which in turn decreases TRIM21-mediated OCT1 ubiquitination and subsequently stabilises OCT1. Consequently, OCT1 stabilisation leads to ALDH1A1expression and promotes cancer stemness. We further showed that the protein expression levels of CSN6, TRIM21 and ALDH1A1 can serve as prognostic markers for human CRC.
conclusionsIn conclusion, we validate a pathway for cancer stemness regulation involving ALDH1A1 levels through the CSN6-TRIM21 axis, which may be utilised as CRC molecular markers and be targeted for therapeutic intervention in cancers.
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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.