ArticleBritish journal of cancer2023
Immunoproteasome inhibition prevents progression of castration-resistant prostate cancer.
Article in British journal of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 13 citations in OpenAlex.
- The role of ER-associated degradation and ER-phagy in health and disease.Signal transduction and targeted therapy · 2026Review
- ONX-0914 Suppresses Hormone-Sensitive Prostate Cancer by Promoting O-GlcNAcylation-Mediated Stabilization of TCF7L1.Oncology research · 2026Article
- Review
- Article
- Immunoproteasome subunits are novel signatures for predicting efficacy of immunotherapy in muscle invasive bladder cancer.Journal of translational medicine · 2025Article
- Trillin inhibits MAP3K11/NF-κB/COX-2 signaling pathways through upregulation of miR-145-5p in castration-resistant prostate cancer.iScience · 2025Article
- From oncogenesis to prognosis: the roles of the immunoproteasome in cancer.Frontiers in immunology · 2025Review
- Rewiring tumor visibility: The immunopeptidome as a dynamic interface between antigen processing, microenvironmental stress, and immune recognition.Frontiers in oncology · 2025Review
- Ubiquitin-proteasome system as a target for anticancer treatment-an update.Archives of pharmacal research · 2023Review
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8 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCastration-resistant prostate cancer (CRPC) is refractory to hormone treatment. This study aims to explore the effect and underlying mechanisms of immunoproteasome inhibition, a novel immunotherapy, on the progression of CRPC.
methodsThe immunoproteasome subunit LMP7 was silenced by using gene knockout or inhibited by the epoxyketone inhibitor ONX 0914 in a mouse CRPC tumour graft model and in interferon-γ-pretreated human CRPC cell lines in vitro.
resultsCRPC tissues reveal a significant "tumour-elicited" Th17-type inflammatory response which induces immunoproteasome subunit expression. LMP7 deficiency in host mice or in CRPC tumour grafts had no effect on the "tumour-elicited" Th17-type inflammatory response and tumour progression. However, the selective LMP7 inhibitor ONX 0914 strongly suppressed the "tumour-elicited" Th17-type inflammatory response and CRPC tumour progression. Treatment of wild-type mice receiving LMP7-deficient CRPC tumour grafts with ONX 0914 further suggested that immunoproteasome inhibition prevents CRPC progression through suppressing IL-17-induced angiogenesis and epithelial-mesenchymal transition via inactivation of COX-2/VEGF-A signalling and β-catenin/Snail signalling. Treatment of LMP7-deficient mice receiving wild-type CRPC tumour grafts with ONX 0914 and inhibition of LMP7 in PC3 and 22Rv.1 cells with ONX 0914 showed that immunoproteasome inhibition also prevents CRPC progression through inducing CRPC cell apoptosis via activation of the unfolded protein response.
conclusionsWe define a critical role of the immunoproteasome in CRPC and propose immunoproteasome inhibition as a promising therapeutic approach to suppress CRPC progression.
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