IL-17RA/CTSK axis mediates H. pylori-induced castration-resistant prostate cancer growth

• Published in: Oncogene Vol. 43; no. 49; pp. 3598 - 3616
• Main Authors: Lin, Guowen, Tian, Feng, Yu, Qiwei, Weng, Xiaoling, Yu, Nanhui, Zhang, Feng, Yi, Chen, Ye, Jian, Ye, Dingwei
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 27.11.2024; Nature Publishing Group
• Subjects: 631/67; 631/80; 64/60; Androgens; Animals; Apoptosis; Castration; Cell Biology; Cell Line, Tumor; Cell Proliferation; Clinical outcomes; Enzyme-linked immunosorbent assay; Epithelial-Mesenchymal Transition; Feces; Gene Expression Regulation, Neoplastic; Genes; Helicobacter Infections - complications; Helicobacter Infections - microbiology; Helicobacter Infections - pathology; Helicobacter pylori; Helicobacter pylori - pathogenicity; Hospitals; Human Genetics; Humans; Hypotheses; Infections; Internal Medicine; Kinases; Macrophages; Macrophages - immunology; Macrophages - metabolism; Macrophages - microbiology; Male; Medical prognosis; Medical research; Medicine; Medicine & Public Health; Metastases; Metastasis; Mice; Microbiota; Oncology; Patients; Polarization; Prostate cancer; Prostatic Neoplasms, Castration-Resistant - genetics; Prostatic Neoplasms, Castration-Resistant - metabolism; Prostatic Neoplasms, Castration-Resistant - microbiology; Prostatic Neoplasms, Castration-Resistant - pathology; Receptors, Interleukin-17 - genetics; Receptors, Interleukin-17 - metabolism; rRNA 16S; Transcriptomes; Urology
• ISSN: 0950-9232; 1476-5594; 1476-5594
• DOI: 10.1038/s41388-024-03169-z

In this investigation, we explored the molecular dynamics guiding the progression of castration-resistant prostate cancer (CRPC) influenced by Helicobacter pylori (H. pylori )-mediated M2 polarization of macrophages through the IL-17RA/CTSK/EMT axis. An 830-patient clinical trial categorized subjects into hormone-sensitive prostate cancer (HSPC) and CRPC groups. H. pylori infection, evaluated by ELISA, exhibited a higher incidence in CRPC patients, impacting overall survival (OS) and progression-free survival. In-depth in vitro and in vivo experiments, including 16S rDNA sequencing, immunohistochemical tests, and transcriptome analysis, unveiled that H. pylori promotes CRPC growth and metastasis by upregulating IL-17RA and CTSK, leading to enhanced EMT. Notably, M2 macrophages emerged as pivotal immune cells influencing CRPC progression. This study uncovers a novel pathway wherein H. pylori enrichment exacerbates CRPC by inducing macrophage M2 polarization, IL-17RA/CTSK expression, and EMT activation, shedding light on a previously unrecognized mechanism contributing to the growth and metastasis of CRPC.