2. Academic Validation
  3. NRP1 promotes prostate cancer progression via modulating EGFR-dependent AKT pathway activation

NRP1 promotes prostate cancer progression via modulating EGFR-dependent AKT pathway activation

  • Cell Death Dis. 2023 Feb 25;14(2):159. doi: 10.1038/s41419-023-05696-1.
Peng Zhang # 1 2,  Liang Chen # 1 2,  Fenfang Zhou 1 2,  Zhiwen He 1 2,  Gang Wang 3 4 5,  Yongwen Luo 6 7 8 9 10
Affiliations

Affiliations

  • 1 Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.
  • 2 Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, China.
  • 3 Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, China. gangwang.uro@whu.edu.cn.
  • 4 Human Genetics Resource Preservation Center of Hubei Province, Wuhan, China. gangwang.uro@whu.edu.cn.
  • 5 Laboratory of Precision Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China. gangwang.uro@whu.edu.cn.
  • 6 Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China. luoywen@whu.edu.cn.
  • 7 Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, China. luoywen@whu.edu.cn.
  • 8 Human Genetics Resource Preservation Center of Hubei Province, Wuhan, China. luoywen@whu.edu.cn.
  • 9 Laboratory of Precision Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China. luoywen@whu.edu.cn.
  • 10 Medical Research Institute, Wuhan University, Wuhan, China. luoywen@whu.edu.cn.
  • # Contributed equally.
PMID: 36841806 DOI: 10.1038/s41419-023-05696-1
Abstract

Prostate Cancer (PCa) is the most common malignant tumor with a high global incidence in males. The mechanism underlying PCa progression is still not clear. This study observed that NRP1 was highly expressed in PCa and associated with poor prognosis in PCa patients. Functionally, NRP1 depletion attenuated the proliferation and migration ability of PCa cells in vitro and in vivo, while NRP1 overexpression promoted PCa cell proliferation and migration. Moreover, it was observed that NRP1 depletion induced G1 phase arrest in PCa cells. Mechanistically, HIF1α is bound to the specific promoter region of NRP1, thereby regulating its transcriptional activation. Subsequently, NRP1 interacted with EGFR, leading to EGFR phosphorylation. This study also provided evidence that the b1/b2 domain of NRP1 was responsible for the interaction with the extracellular domain of EGFR. Moreover, EGFR mediated NRP1-induced activation of the Akt signaling pathway, which promoted the malignant progression of PCa. In addition, the administration of NRP1 inhibitor EG01377 significantly inactivated the EGFR/Akt signaling axis, thereby suppressing PCa progression. In conclusion, the findings from this study highlighted the molecular mechanism underlying NRP1 expression in PCa and provide a potential predictor and therapeutic target for clinical prognosis and treatment of PCa.

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