ArticleCancers2020
Ubiquitin-Specific Protease 21 Promotes Colorectal Cancer Metastasis by Acting as a Fra-1 Deubiquitinase.
Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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The trial behind it
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Who cites it
31 citing papers in PubMed.
- USP21 functions as an oncogenic regulator of the Mdm2-p53 axis in colorectal cancer.Cell death discovery · 2026Article
- A prognostic nomogram for colorectal cancer based on ubiquitin-specific protease 21 expression: a retrospective cohort study.Frontiers in molecular biosciences · 2026Article
- Targeting the FOSL1/IKKα positive feedback loop attenuates glioblastoma malignancyTheranostics · 2026Article
- Ubiquitin-specific proteases as key regulators in the malignant progression and therapy resistance of colorectal cancer: current insights and future perspectives.Discover oncology · 2025Review
- USP15 Drives NSCLC Progression and Chemoresistance, Potentially via Regulation of the U2-Type Spliceosomal Complex.Cancer medicine · 2025Article
- USP21-EGFR signaling axis is functionally implicated in metastatic colorectal cancer.Cell death discovery · 2024Article
- Emerging roles of deubiquitinating enzymes in actin cytoskeleton and tumor metastasis.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- USP21-mediated G3BP1 stabilization accelerates proliferation and metastasis of esophageal squamous cell carcinoma via activating Wnt/β-Catenin signaling.Oncogenesis · 2024Article
- FOSL1's Oncogene Roles in Glioma/Glioma Stem Cells and Tumorigenesis: A Comprehensive Review.International journal of molecular sciences · 2024Review
- Ubiquitin-specific protease 21 promotes tumorigenicity and stemness of colorectal cancer by deubiquitinating and stabilizing ZEB1.World journal of gastrointestinal oncology · 2024Article
- Comprehensive analysis of the role of ubiquitin-specific peptidases in colorectal cancer: A systematic review.World journal of gastrointestinal oncology · 2024Article
- Fra-1 affects chemotherapy sensitivity by inhibiting ferroptosis in gastric cancer cells.Cancer drug resistance (Alhambra, Calif.) · 2024Article
- PARP7-mediated ADP-ribosylation of FRA1 promotes cancer cell growth by repressing IRF1- and IRF3-dependent apoptosis.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Hedyotis diffusa-Sculellaria barbata (HD-SB) suppresses the progression of colorectal cancer cells via the hsa_circ_0039933/hsa-miR-204-5p/wnt11 axis.Scientific reports · 2023Article
- Promotive role of USP29-mediated deubiquitination in malignant proliferation of colorectal cancer cells via the KIAA1429/SOX8 axis.Biomolecules & biomedicine · 2023Article
- Discovery and Characterization of BAY-805, a Potent and Selective Inhibitor of Ubiquitin-Specific Protease USP21.Journal of medicinal chemistry · 2023Article
- Review
- Gallic acid induces T-helper-1-like TJournal for immunotherapy of cancer · 2022Article
- The Fra-1/AP-1 Oncoprotein: From the "Undruggable" Transcription Factor to Therapeutic Targeting.Cancers · 2022Review
- Pro-apoptotic and anti-apoptotic regulation mediated by deubiquitinating enzymes.Cellular and molecular life sciences : CMLS · 2022Review
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Fos-related-antigen-1 (Fra-1), a member of the activator protein-1 (AP-1) transcription factor superfamily, has an essential role in cancer progress and metastasis and Fra-1 is considered a therapeutic target in metastatic cancer including metastatic colorectal cancer (mCRC). However, its regulation at protein level has not yet been clearly elucidated. We found that ubiquitin-specific protease 21 (USP21) increases Fra-1 stability by deubiquitinating Fra-1 and enhances the expression of Fra-1 target genes in colon cancer cells. We also showed that USP21 controlled Fra-1-dependent migration and invasion activities. The oncogenic property of USP21 was confirmed by a significant reduction in liver metastasis when USP21-knockdown cancer cells were injected intrasplenically into mice. Consistently, clinicopathological analysis of colorectal cancer patients revealed a correlation of USP21 expression with high-grade carcinoma and life span. These results demonstrate that USP21 enhances Fra-1 stability and AP-1 target gene expression by deubiquitinating Fra-1. Therefore, USP21 is considered an attractive therapeutic target in mCRC with high Fra-1 expression.
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