ArticleCell death & disease2025
Mechanical signal modulates prostate cancer immune escape by USP8-mediated ubiquitination-dependent degradation of PD-L1 and MHC-1.
Article in Cell death & disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Synergistic Regulation of Tumor Immunity by Integrins and Lectins: From Molecular Mechanisms to Dual-Targeted Therapy.International journal of molecular sciences · 2026Review
- Canonical and noncanonical autophagy in immunity.Immunity · 2026Review
- Article
- Nanomedicine targeting ECM stiffness: restoring mechanical homeostasis for cancer immunotherapy.Materials today. Bio · 2026Review
- Systemic and cardiac pathology induced by a clinically relevant USP8 activating mutation.Disease models & mechanisms · 2026Article
- Core regulatory mechanisms of the PD-L1 axis and clinical strategies for immune escape and immunotherapy response in nasopharyngeal carcinoma.Translational oncology · 2026Review
- Identification of a novel ion channel-related gene signature to predict prognosis and immune response of gastric cancer.Translational cancer research · 2026Article
- Biomimetic nanodecoys remodel the mechano-immune microenvironment to potentiate checkpoint blockade in colorectal cancer.Journal of nanobiotechnology · 2026Article
- Deubiquitinase USP8 regulates the spindle assembly checkpoint in oocytes.Science advances · 2026Article
- Role of autophagy in tumorigenesis and drug resistance: molecular mechanisms and therapeutic targets.Molecular biomedicine · 2026Review
- Review
- Research progress on tumor extracellular matrix stiffness and immunosuppression.Frontiers in immunology · 2026Review
- Mechanical properties of the tumor microenvironment: drivers of immunotherapy resistance in solid tumors.Frontiers in immunology · 2026Review
- OTUB2/ALYREF axis modulates the docetaxel resistance of castration-resistant prostate cancer via upregulating ABCG4-mediated drug efflux.International journal of biological sciences · 2026Article
- YAP1 converts circELP2-mediated biochemical signals to mechanical forces through promoting cytoskeleton remodeling in pulmonary fibrosis.International journal of biological sciences · 2026Article
- Small molecules targeting the PD-1/PD-L1 axis for cancer immunotherapy.Theranostics · 2026Review
- Regulatory roles of five key USP family deubiquitinases in cancer: from mechanisms to targeted therapy advances.Frontiers in pharmacology · 2026Review
- The Quartet of Core Oncogenic Drivers in Neuroendocrine Prostate Cancer: Multi-Omics Dataset Integration to Forge a Translational Link Between Biology and Precision Therapy.International journal of biological sciences · 2026Review
- Programmed Cell Death in Urological Cancers: Orchestrating the Immune Microenvironment and Immunotherapy.Oncology research · 2026Review
- Lactylation-related gene signatures for prognosis and treatment response prediction in radiation-resistant non-small cell lung cancer.Discover oncology · 2025Article
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The tumor environment of prostate cancer (PCa) tissues of high Gleason score has been proved to be more immune suppressive and has higher extracellular matrix (ECM) stiffness, but whether ECM mechanical stiffness is the cause of higher ability of invasiveness and immune escape of PCa with high Gleason score remains uncertain. In this study, we showed that higher polyacrylamide hydrogels (PAAG) stiffness resulted in the progression and immune escape of PCa via integrin β1/FAK/YAP axis. The translocation of YAP into cell nucleus to bind to TEAD2 promoted the transcriptional activation of USP8. NBR1 could be ubiquitinated, and then degraded, via interacting with P62/SQSTM1 and through autophagy-lysosome pathway. Increased expression of USP8 promoted the abundance of NBR1 via K63-linked de-ubiquitination and PD-L1 via K48-linked de-ubiquitination in response to high PAAG stiffness. NBR1-mediated selective autophagy accelerated the degradation of MHC-1 of PCa. The USP8 inhibitor presented a potential application value in sensitizing immunotherapy of PCa. Taken together, we identified a USP8-mediated de-ubiquitination mechanism that involves in the process of high PAAG stiffness-mediated high expression of PD-L1 and low expression of MHC-1 of PCa cells, which provided a rationale of immunotherapy sensitization of PCa via USP8 inhibition.
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