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

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

  • Oncogene. 2024 Nov;43(49):3598-3616. doi: 10.1038/s41388-024-03169-z.
Guowen Lin # 1 2 3,  Feng Tian # 4,  Qiwei Yu # 5,  Xiaoling Weng 6,  Nanhui Yu 7,  Feng Zhang 4,  Chen Yi 8,  Jian Ye 9,  Dingwei Ye 10 11 12
Affiliations

Affiliations

  • 1 Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China. linguowen@fudan.edu.cn.
  • 2 Shanghai Genitourinary Cancer Institute, Shanghai, 200032, China. linguowen@fudan.edu.cn.
  • 3 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. linguowen@fudan.edu.cn.
  • 4 Department Of Urology, Shanghai Eighth People's Hospital, Shanghai, 200235, China.
  • 5 Department of Urology, Kunshan Hospital of Traditional Chinese Medicine, Suzhou, 215399, China.
  • 6 State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200001, China.
  • 7 Department of Gastrointestinal Surgery, the Second Xiangya Hospital of Central South University, Changsha, 410011, China.
  • 8 Department of Urology, Changsha Central Hospital Affiliated to University of South China, Changsha, 410000, China.
  • 9 Department of Immuno-Oncology, Beckman Research Institute of the City of Hope, Duarte, CA, USA.
  • 10 Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China. dwyeli@163.com.
  • 11 Shanghai Genitourinary Cancer Institute, Shanghai, 200032, China. dwyeli@163.com.
  • 12 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. dwyeli@163.com.
  • # Contributed equally.
PMID: 39424989 DOI: 10.1038/s41388-024-03169-z
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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