ArticleClinical and translational medicine2024
Insight into prostate cancer osteolytic metastasis by RelB coordination of IL-8 and S100A4.
Article in Clinical and translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- RelB/ILF2-GM-CSF loop sustains tumor-MDSC communication in prostate cancer immunosuppression.Cell death & disease · 2026Article
- RELB Overexpression Induced by DNA Hypomethylation Contributes to Perioperative Immunotherapy Resistance in Resectable Esophageal Squamous Cell Carcinoma by Modulating the mregDC-Treg Axis.Cancer medicine · 2026Article
- Bone and Infections: An Osteoimmunological Interplay.International journal of molecular sciences · 2026Review
- Early Detection of Prostate Cancer Using Novel ELISA-Based Biomarkers: Insights into Inflammatory and Tumor-Specific Pathways.Asian Pacific journal of cancer prevention : APJCP · 2025Article
- Prostate Cancer Bone Metastasis: Molecular Mechanisms of Tumor and Bone Microenvironment.Cancer management and research · 2025Review
- Insight into prostate cancer osteolytic metastasis by RelB coordination of IL-8 and S100A4.Clinical and translational medicine · 2024Article
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Authors and funding
13 authors.
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Abstract
backgroundAlthough RANK-LRANK interaction is essential for osteoclastogenesis, the mechanisms by which cancer cells invade bone tissues and initiate osteolytic metastasis remain unclear. Here, we show that the hyperactivation of RelB fosters prostate cancer (PCa) osteolytic metastasis by coordinating interleukin-8 (IL-8) and calcium-binging protein A4 (S100A4).
methodsThe factors promoting PCa bone metastasis were investigated in sera from PCa patients and tumour tissues derived from nude mice using immunohistochemical analysis and enzyme-linked immunosorbent assays (ELISA). Cell mobility and mineralization were quantified using BioStation CT and Osteolmage assay. The relative cistrome was investigated in advanced PCa cells by standard transcriptional analyses, including the luciferase reporter response, site-directed mutagenesis, and chromatin immunoprecipitation (ChIP) assay. PCa cell-initiated tumour formation, expansion, and bone metastasis were validated in mice using multiple approaches, including orthotopic, intraskeletal, and caudal arterial implantation models.
resultsIL-8 and S100A4 correlated with patient Gleason scores and bone metastasis. RelB upregulated IL-8, facilitating androgen receptor (AR)-independent growth. RelB-Sp1 interaction enhanced epithelial-mesenchymal transition (EMT) by activating Snail and Twist. RelB-NFAT1c super-enhancer upregulated S100A4 in the organization of the cytoskeleton and bone metastasis. The RelB-IL-8-S100A4 signalling axis was confirmed to promote osteolytic metastasis in nude mice.
conclusionRelB-IL-8 reciprocally promoted EMT by activating inflammatory signalling and inactivating AR signalling. IL-8 is essential for provoking PCa metastasis but insufficient to drive bone metastasis. IL-8-S100A4 cooperation was necessary for metastatic cells to target the bone. HIGHLIGHTS: RelB activates inflammatory signalling by upregulating IL-8 and suppressing AR. RelB upregulates S100A4 by cooperating with NFATC1. IL-8 boosts EMT by activating Snail 1 and Twist 1, and S100A4 exacerbates osteolytic metastasis via calcium consumption. RelB harnesses IL-8 and S100A4 to drive PCa osteolytic metastasis.
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