ArticleThe EMBO journal2022
USP8 promotes cancer progression and extracellular vesicle-mediated CD8+ T cell exhaustion by deubiquitinating the TGF-β receptor TβRII.
Article in The EMBO journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 84 citations in OpenAlex.
- The molecular mechanisms of platelets in tumor invasion and metastasis: a controversial role.Cancer biology & therapy · 2026Review
- It takes two to tango: the intersection of deubiquitinases and mMolecular cancer · 2026Review
- Blocking Extracellular Cyclophilin A-Mediated Adhesion Protects Against Bacterial Infection.MedComm · 2026Article
- Extracellular vesicles in breast cancer metastasis: functional insights and advances in single-EV analysis.Cancer metastasis reviews · 2026Review
- Identification of Key Indicators in the Adverse Outcome Pathway for Genetic Damage Induced by Chromate Exposure: A Machine Learning-Based Cross-Sectional Study.Environment & health (Washington, D.C.) · 2026Article
- Article
- TUFT1 stabilizes TGF-β receptor II protein and facilitates activation of hepatic stellate cells into metastasis-promoting myofibroblasts.Cell death and differentiation · 2026Article
- The updated role of exosomes in cancer diagnosis and therapy.Discover oncology · 2026Review
- Evaluation of human epidermal growth factor receptor 2 (HER2)-related genes revealed that HER2-antibody-drug conjugate (ADC) drugs confer clinical benefits to Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer patients.Translational andrology and urology · 2026Article
- Automated Cryo-EM and Supervised Machine Learning Enable Reproducible Characterization of Extracellular Vesicles and Co-Isolating Particles.Journal of extracellular vesicles · 2026Article
- Sphingosine-1-phosphate promotes CD8 T cell exhaustion in breast cancer via exosomal transfer of TGFBR2.Cell death & disease · 2026Article
- Deubiquitinase USP8 regulates the spindle assembly checkpoint in oocytes.Science advances · 2026Article
- The Ubiquitin-Specific Protease Family: Master Regulators of Renal Fibrosis Pathogenesis and Therapeutic Targets.International journal of molecular sciences · 2026Review
- TGF-β in tumor development and progression: mechanisms and therapeutics.Molecular biomedicine · 2026Review
- Endothelial USP8 is essential for angiogenesis.Angiogenesis · 2026Article
- Positive feedback regulation between USP8 and Hippo/YAP axis drives triple-negative breast cancer progression.Cell death & disease · 2026Article
- Revitalizing T cells: breakthroughs and challenges in overcoming T cell exhaustion.Signal transduction and targeted therapy · 2026Review
- USP20, a Super-enhancer Regulated Gene, Promotes Acute Myeloid Leukemia Progression through CTNNB1 Deubiquitination.International journal of biological sciences · 2026Article
- Single-Cell Multiomics Integration Reveals Cell Trajectories and Regulatory Networks in Breast Cancer Progression.International journal of genomics · 2026Article
- Post-translational modifications in CD8Frontiers in immunology · 2026Review
11 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TGF-β signaling is a key player in tumor progression and immune evasion, and is associated with poor response to cancer immunotherapies. Here, we identified ubiquitin-specific peptidase 8 (USP8) as a metastasis enhancer and a highly active deubiquitinase in aggressive breast tumors. USP8 acts both as a cancer stemness-promoting factor and an activator of the TGF-β/SMAD signaling pathway. USP8 directly deubiquitinates and stabilizes the type II TGF-β receptor TβRII, leading to its increased expression in the plasma membrane and in tumor-derived extracellular vesicles (TEVs). Increased USP8 activity was observed in patients resistant to neoadjuvant chemotherapies. USP8 promotes TGF-β/SMAD-induced epithelial-mesenchymal transition (EMT), invasion, and metastasis in tumor cells. USP8 expression also enables TβRII+ circulating extracellular vesicles (crEVs) to induce T cell exhaustion and chemoimmunotherapy resistance. Pharmacological inhibition of USP8 antagonizes TGF-β/SMAD signaling, and reduces TβRII stability and the number of TβRII+ crEVs to prevent CD8+ T cell exhaustion and to reactivate anti-tumor immunity. Our findings not only reveal a novel mechanism whereby USP8 regulates the cancer microenvironment but also demonstrate the therapeutic advantages of engineering USP8 inhibitors to simultaneously suppress metastasis and improve the efficacy of cancer immunotherapy.
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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.