ArticleCell death & disease2021
Non-apoptotic function of caspase-8 confers prostate cancer enzalutamide resistance via NF-κB activation.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- A mechanism of target mRNA selection and activity regulation in meiosis-related RBM46-MEIOC-YTHDC2 complex.iScience · 2026Article
- The paradigm-shifting roles of caspase-3 in cancer: from death towards resuscitation.Cancer cell international · 2026Review
- Large-Scale Transcriptome Profiling and Network Pharmacology Analysis Reveal the Multi-Target Inhibitory Mechanism of Modified Guizhi Fuling Decoction in Prostate Cancer Cells.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Multi-omics Analysis Sheds Light on the Extracellular Role of PCMT1.Journal of proteome research · 2025Article
- Multi-Omics Analysis of the Anoikis GeneBiomedicines · 2025Article
- Berberine decreases S100B generation to regulate gut vascular barrier permeability in mice with burn injury.Pharmaceutical biology · 2024Article
- Versatile function of NF-ĸB in inflammation and cancer.Experimental hematology & oncology · 2024Review
- Targeting caspase-8: a new strategy for combating hepatocellular carcinoma.Frontiers in immunology · 2024Review
- Apoptotic proteins with non-apoptotic activity: expression and function in cancer.Apoptosis : an international journal on programmed cell death · 2023Review
- Quercetin is a Potential Therapy for Rheumatoid Arthritis via Targeting Caspase-8 Through Ferroptosis and Pyroptosis.Journal of inflammation research · 2023Article
- Short-term assays for mesenchymal stromal cell immunosuppression of T-lymphocytes.Frontiers in immunology · 2023Article
- Enzalutamide Induces Apoptotic Insults to Human Drug-Resistant and -Sensitive Glioblastoma Cells via an Intrinsic Bax-Mitochondrion-Cytochrome C Caspase Cascade Activation Pathway.Molecules (Basel, Switzerland) · 2022Article
- The Novel Protein ADAMTS16 Promotes Gastric Carcinogenesis by Targeting IFI27 through the NF-κb Signaling Pathway.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Caspase-8 is a unique member of caspases with a dual role in cell death and survival. Caspase-8 expression is often lost in some tumors, but increased in others, indicating a potential pro-survival function in cancer. By analyzing transcriptome of enzalutamide-resistant prostate cancer cells, we found that resistance was conferred by a mild caspase-8 upregulation that in turn led to NF-κB activation and the subsequent upregulation of the downstream IL-8. Mechanistically, we found that the pro-survival and enzalutamide-resistance-promoting features of caspase-8 were independent of its proteolytic activity, using a catalytically-inactive caspase-8 mutant. We further demonstrated that caspase-8 pro-apoptotic function was inhibited via cFLIP binding. Moreover, high caspase-8 expression was correlated with a worse prognosis in prostate cancer patients. Collectively, our work demonstrates that enzalutamide-resistance is mediated by caspase-8 upregulation and the consequent increase in NF-κB/IL-8 mediated survival signaling, highlighting caspase-8 and NF-κB as potential therapeutic targets to overcome enzalutamide-resistance in CRPC.
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