2. Academic Validation
  3. HGF/c-Met pathway facilitates the perineural invasion of pancreatic cancer by activating the mTOR/NGF axis

HGF/c-Met pathway facilitates the perineural invasion of pancreatic cancer by activating the mTOR/NGF axis

  • Cell Death Dis. 2022 Apr 21;13(4):387. doi: 10.1038/s41419-022-04799-5.
Tao Qin 1,  Ying Xiao 1,  Weikun Qian 1,  Xueni Wang 1,  Mengyuan Gong 1,  Qiqi Wang 1,  Rui An 1,  Liang Han 1 2,  Wanxing Duan 1 2,  Qingyong Ma 3 4 5,  Zheng Wang 6 7 8
Affiliations

Affiliations

  • 1 Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
  • 2 Centre for Pancreatic Diseases of Xi'an Jiaotong University, Xi'an, China.
  • 3 Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. qyma56@mail.xjtu.edu.cn.
  • 4 Centre for Pancreatic Diseases of Xi'an Jiaotong University, Xi'an, China. qyma56@mail.xjtu.edu.cn.
  • 5 Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Xi'an, China. qyma56@mail.xjtu.edu.cn.
  • 6 Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. zheng.wang11@mail.xjtu.edu.cn.
  • 7 Centre for Pancreatic Diseases of Xi'an Jiaotong University, Xi'an, China. zheng.wang11@mail.xjtu.edu.cn.
  • 8 Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Xi'an, China. zheng.wang11@mail.xjtu.edu.cn.
PMID: 35449152 DOI: 10.1038/s41419-022-04799-5
Abstract

Perineural invasion (PNI) is a pathologic feature of pancreatic Cancer and is associated with poor outcomes, metastasis, and recurrence in pancreatic Cancer patients. However, the molecular mechanism of PNI remains unclear. The present study aimed to investigate the mechanism that HGF/c-Met pathway facilitates the PNI of pancreatic Cancer. In this study, we confirmed that c-Met expression was correlated with PNI in pancreatic Cancer tissues. Activating the HGF/c-Met signaling pathway potentiated the expression of nerve growth factor (NGF) to recruit nerves and promote the PNI. Activating the HGF/c-Met signaling pathway also enhanced the migration and invasion ability of Cancer cells to facilitate Cancer cells invading nerves. Mechanistically, HGF/c-Met signaling pathway can active the mTOR/NGF axis to promote the PNI of pancreatic Cancer. Additionally, we found that knocking down c-Met expression inhibited Cancer cell migration along the nerve, reduced the damage of the sciatic nerve caused by Cancer cells and protected the function of the sciatic nerve in vivo. Taken together, our findings suggest a supportive mechanism of the HGF/c-Met signaling pathway in promoting PNI by activating the mTOR/NGF axis in pancreatic Cancer. Blocking the HGF/c-Met signaling pathway may be an effective target for the treatment of PNI.

Figures
Products