1. Academic Validation
  2. Natriuretic peptide receptor a promotes gastric malignancy through angiogenesis process

Natriuretic peptide receptor a promotes gastric malignancy through angiogenesis process

  • Cell Death Dis. 2021 Oct 20;12(11):968. doi: 10.1038/s41419-021-04266-7.
Zheng Li  # 1 Hao Fan  # 1 Jiacheng Cao  # 1 Guangli Sun  # 1 Sen Wang 1 Jialun Lv 1 Zhe Xuan 1 Yiwen Xia 1 Linjun Wang 1 Diancai Zhang 1 Hao Xu 1 Zekuan Xu 2 3
Affiliations

Affiliations

  • 1 Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, No.300, Guangzhou Road, Nanjing, 210029, Jiangsu Province, China.
  • 2 Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, No.300, Guangzhou Road, Nanjing, 210029, Jiangsu Province, China. xuzekuan@njmu.edu.cn.
  • 3 Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 210029, Jiangsu Province, China. xuzekuan@njmu.edu.cn.
  • # Contributed equally.
Abstract

Gastric Cancer (GC) ranks the third among global cancer-related mortality, especially in East Asia. Angiogenesis plays an important role in promoting tumor progression, and clinical trials have demonstrated that anti-angiogenesis therapy is effective in GC management. Natriuretic peptide receptor A (NPRA) functions significantly in promoting GC development and progression. Whether NPRA can promote angiogenesis of GC remains unclear. Tumor samples collection and immunohistochemical experiment showed that the expression of NPRA was positively correlated with the expression of CD31 and vessel density. In vivo and in vitro analysis showed that NPRA could promote GC-associated angiogenesis and tumor metastasis. Results of Co-IP/MS showed that NPRA could prevent HIF-1α from being degraded by binding to HIF-1α. Protection of HIF-1α improved VEGF levels and thus promoted angiogenesis. In summary, NPRA protected HIF-1α from proteolysis by binding to HIF-1α, increased the expression of HIF-1α, and promoted GC angiogenesis. This study has discovered a new mechanism for NPRA to promote gastric Cancer development and a new regulatory mechanism for HIF-1α.

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