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

IF 6.9 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Oncogene Pub Date : 2024-10-18 DOI:10.1038/s41388-024-03169-z

Guowen Lin, Feng Tian, Qiwei Yu, Xiaoling Weng, Nanhui Yu, Feng Zhang, Chen Yi, Jian Ye, Dingwei Ye

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Abstract

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.

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IL-17RA/CTSK轴介导幽门螺杆菌诱导的耐阉割前列腺癌生长

在这项研究中，我们探讨了幽门螺杆菌（H. pylori）通过IL-17RA/CTSK/EMT轴介导的巨噬细胞M2极化对去势抵抗性前列腺癌（CRPC）进展的分子动力学影响。一项有 830 名患者参加的临床试验将受试者分为激素敏感性前列腺癌 (HSPC) 组和 CRPC 组。通过酶联免疫吸附试验（ELISA）评估，幽门螺杆菌感染在CRPC患者中的发病率较高，影响总生存期（OS）和无进展生存期。深入的体外和体内实验，包括16S rDNA测序、免疫组化检测和转录组分析，揭示了幽门螺杆菌通过上调IL-17RA和CTSK促进CRPC生长和转移，导致EMT增强。值得注意的是，M2巨噬细胞成为影响CRPC进展的关键免疫细胞。这项研究发现了一种新的途径，即幽门螺杆菌富集通过诱导巨噬细胞M2极化、IL-17RA/CTSK表达和EMT活化来加剧CRPC，从而揭示了一种以前未被认识到的导致CRPC生长和转移的机制。

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来源期刊

Oncogene 医学-生化与分子生物学

CiteScore

15.30

自引率

1.20%

发文量

404

审稿时长

1 months

期刊介绍： Oncogene is dedicated to advancing our understanding of cancer processes through the publication of exceptional research. The journal seeks to disseminate work that challenges conventional theories and contributes to establishing new paradigms in the etio-pathogenesis, diagnosis, treatment, or prevention of cancers. Emphasis is placed on research shedding light on processes driving metastatic spread and providing crucial insights into cancer biology beyond existing knowledge. Areas covered include the cellular and molecular biology of cancer, resistance to cancer therapies, and the development of improved approaches to enhance survival. Oncogene spans the spectrum of cancer biology, from fundamental and theoretical work to translational, applied, and clinical research, including early and late Phase clinical trials, particularly those with biologic and translational endpoints.