The AKT-independent MET-V-ATPase-MTOR axis suppresses liver cancer vaccination

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Xing Huang1,2,3,4, Xingyuan Xu5,6,7, Xun Wang5,6,7

  • 1Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang, China. huangxing66@zju.edu.cn.

Signal Transduction and Targeted Therapy
|August 9, 2020
PubMed

Insights

Targeting the MET-V-ATPase-MTOR pathway enhances liver cancer vaccine efficacy. This study reveals hepatocyte growth factor receptor (MET) interaction with V-ATPase and MTOR suppresses tumor immunity, offering new strategies for cancer prevention.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Hepatocellular carcinoma (liver cancer) lacks effective vaccines despite treatment advances.
  • Hepatocyte growth factor receptor (MET), also known as HGFR, role in liver cancer immunity is unclear.

Purpose of the Study:

  • Investigate MET's regulatory effect on liver cancer vaccines.
  • Elucidate the mechanism of MET in modulating liver cancer immunogenicity.
  • Explore MET-V-ATPase-MTOR axis as a therapeutic target.

Main Methods:

  • Assessed MET expression in mouse and human liver cancer.
  • Depleted MET in mice to evaluate vaccine efficacy.
  • Investigated MET's interaction with V-ATPase and MTOR signaling pathways.

Main Results:

  • MET expression correlates with liver cancer immunogenicity in mice and humans.
  • MET depletion significantly enhances chemotherapy-based anti-liver cancer vaccine efficacy.
  • MET suppresses liver cancer immunity via interaction with V-ATPase and MTOR activation, independent of PI3K-AKT.

Conclusions:

  • Targeting the MET-V-ATPase-MTOR axis improves chemotherapy-based liver cancer vaccination.
  • MET is a critical regulator of liver cancer immunogenicity.
  • This axis presents a promising strategy for developing MET-associated drug candidates for cancer prevention.

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