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
  • 1. Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China. [email protected].
  • 2. Shanghai Genitourinary Cancer Institute, Shanghai, 200032, China. [email protected].
  • 3. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. [email protected].
  • 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. [email protected].
  • 11. Shanghai Genitourinary Cancer Institute, Shanghai, 200032, China. [email protected].
  • 12. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. [email protected].
  • # 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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