{"title":"通过 RelB 协调 IL-8 和 S100A4 透视前列腺癌的溶骨转移","authors":"Wenbo Sun, Kenny Xu, Xiao Li, Peipei Qian, Fan Xu, Yanyan Zhang, Xiumei Wang, Zhi Xu, Jiaji Ding, Xinyu Xu, Xiaowei Wei, Qin Jiang, Yong Xu","doi":"10.1002/ctm2.70058","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Although 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).</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>The 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.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>IL-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.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>RelB-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.</p>\n </section>\n \n <section>\n \n <h3> Highlights</h3>\n \n <div>\n <ul>\n \n <li>RelB activates inflammatory signalling by upregulating IL-8 and suppressing AR.</li>\n \n <li>RelB upregulates S100A4 by cooperating with NFATC1.</li>\n \n <li>IL-8 boosts EMT by activating Snail 1 and Twist 1, and S100A4 exacerbates osteolytic metastasis via calcium consumption.</li>\n \n <li>RelB harnesses IL-8 and S100A4 to drive PCa osteolytic metastasis.</li>\n </ul>\n </div>\n </section>\n </div>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"14 10","pages":""},"PeriodicalIF":7.9000,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.70058","citationCount":"0","resultStr":"{\"title\":\"Insight into prostate cancer osteolytic metastasis by RelB coordination of IL-8 and S100A4\",\"authors\":\"Wenbo Sun, Kenny Xu, Xiao Li, Peipei Qian, Fan Xu, Yanyan Zhang, Xiumei Wang, Zhi Xu, Jiaji Ding, Xinyu Xu, Xiaowei Wei, Qin Jiang, Yong Xu\",\"doi\":\"10.1002/ctm2.70058\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>Although 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).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>The 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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>IL-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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p>RelB-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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Highlights</h3>\\n \\n <div>\\n <ul>\\n \\n <li>RelB activates inflammatory signalling by upregulating IL-8 and suppressing AR.</li>\\n \\n <li>RelB upregulates S100A4 by cooperating with NFATC1.</li>\\n \\n <li>IL-8 boosts EMT by activating Snail 1 and Twist 1, and S100A4 exacerbates osteolytic metastasis via calcium consumption.</li>\\n \\n <li>RelB harnesses IL-8 and S100A4 to drive PCa osteolytic metastasis.</li>\\n </ul>\\n </div>\\n </section>\\n </div>\",\"PeriodicalId\":10189,\"journal\":{\"name\":\"Clinical and Translational Medicine\",\"volume\":\"14 10\",\"pages\":\"\"},\"PeriodicalIF\":7.9000,\"publicationDate\":\"2024-10-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.70058\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical and Translational Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/ctm2.70058\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical and Translational Medicine","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/ctm2.70058","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Insight into prostate cancer osteolytic metastasis by RelB coordination of IL-8 and S100A4
Background
Although 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).
Methods
The 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.
Results
IL-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.
Conclusion
RelB-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.
期刊介绍：
Clinical and Translational Medicine (CTM) is an international, peer-reviewed, open-access journal dedicated to accelerating the translation of preclinical research into clinical applications and fostering communication between basic and clinical scientists. It highlights the clinical potential and application of various fields including biotechnologies, biomaterials, bioengineering, biomarkers, molecular medicine, omics science, bioinformatics, immunology, molecular imaging, drug discovery, regulation, and health policy. With a focus on the bench-to-bedside approach, CTM prioritizes studies and clinical observations that generate hypotheses relevant to patients and diseases, guiding investigations in cellular and molecular medicine. The journal encourages submissions from clinicians, researchers, policymakers, and industry professionals.
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
