ArticleCancers2020
The Deubiquitinase USP4 Stabilizes Twist1 Protein to Promote Lung Cancer Cell Stemness.
Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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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
34 citing papers in PubMed, 45 citations in OpenAlex.
- USP4 promotes non-small cell lung cancer tumorigenesis by antagonizing CNOT4-mediated degradation of PAF1.Respiratory research · 2026Article
- Regulatory roles of five key USP family deubiquitinases in cancer: from mechanisms to targeted therapy advances.Frontiers in pharmacology · 2026Review
- Pathological role of deubiquitinating enzymes in lung cancer: recent insights and advances.American journal of cancer research · 2026Review
- GBP2 regulates lung cancer progression through STAT1 and impacts glycolysis.Clinical and experimental medicine · 2025Article
- Lactylation-driven USP4-mediated ANXA2 stabilization and activation promotes maintenance and radioresistance of glioblastoma stem cells.Cell death and differentiation · 2025Article
- AKT and DUBs: a bidirectional relationship.Cellular & molecular biology letters · 2025Review
- USP4 promotes proliferation and metastasis in human lung adenocarcinoma.Scientific reports · 2025Article
- Evodiamine inhibits colorectal cancer cell stemness by disturbing ubiquitin specific protease 4 mediated SOX9 stabilization.Discover oncology · 2025Article
- A novel USP4 inhibitor that suppresses colorectal cancer stemness by promoting β-catenin and Twist1 degradation.Journal of translational medicine · 2025Article
- Role of Ubiquitin-regulated EMT in Cancer Metastasis and Chemoresistance.International journal of biological sciences · 2025Review
- USP4 promotes PTC progression by stabilizing LDHA and activating the MAPK and AKT signaling pathway.Aging · 2024Article
- Emerging roles of deubiquitinating enzymes in actin cytoskeleton and tumor metastasis.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- ASB6 as an Independent Prognostic Biomarker for Colorectal Cancer Progression Involves Lymphatic Invasion and Immune Infiltration.Journal of Cancer · 2024Article
- Deubiquitylating Enzymes in Cancer and Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- FBXO3 stabilizes USP4 and Twist1 to promote PI3K-mediated breast cancer metastasis.PLoS biology · 2023Article
- USP4 promotes the proliferation, migration, and invasion of esophageal squamous cell carcinoma by targeting TAK1.Cell death & disease · 2023Article
- USP32 deubiquitinase: cellular functions, regulatory mechanisms, and potential as a cancer therapy target.Cell death discovery · 2023Review
- USP51 promotes non-small cell lung carcinoma cell stemness by deubiquitinating TWIST1.Journal of translational medicine · 2023Article
- Ubiquitin-proteasome system as a target for anticancer treatment-an update.Archives of pharmacal research · 2023Review
- Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Lung cancer stem cells (CSCs) play a pivotal role in tumor development, drug resistance, metastasis and recurrence of lung cancer. Thus, it is of great importance to study the mechanism by which CSCs are regulated. In this study, we demonstrate that the deubiquitinase USP4 is critically important in promoting lung cancer stemness. Silencing of USP4 leads to reduction of Oct4 and Sox2 expression, decreased CD133+ cell population and inhibition of tumorsphere formation. Conversely, ectopic expression of USP4 significantly enhances lung cancer cell stemness, which is effectively rescued by simultaneous silencing of Twist1. Mechanistically, we identified USP4 as a novel deubiquitinase of Twist1. USP4 binds to, deubiquitinates and stabilizes Twist1 protein. Furthermore, we show that USP4 expression is elevated in human lung cancer specimens and is positively correlated with Twist1 expression. High expression of USP4/Twist1 is associated with poor clinical outcomes of lung cancer patients. Together, this study highlights an important role for USP4 in lung cancer stemness and suggests USP4 as a potential target for lung cancer diagnosis and treatment.
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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 Socratic graph.