1. Academic Validation
  2. c-Met up-regulates the expression of PD-L1 through MAPK/NF-κBp65 pathway

c-Met up-regulates the expression of PD-L1 through MAPK/NF-κBp65 pathway

  • J Mol Med (Berl). 2022 Apr;100(4):585-598. doi: 10.1007/s00109-022-02179-2.
Ruyue Xu  # 1 2 Xinkuang Liu  # 1 3 Amin Li  # 1 2 Li Song  # 1 2 Jiaojiao Liang  # 1 2 Jiafeng Gao  # 1 2 Xiaolong Tang 4 5
Affiliations

Affiliations

  • 1 Medical School, Anhui University of Science & Technology, Huainan, 232001, China.
  • 2 Institute of Environmentally-Friendly Materials and Occupational Health, Anhui University of Science and Technology (Wuhu), Wuhu, 241003, China.
  • 3 Clinical Laboratory Medicine, First Affiliated Hospital, Anhui University of Science & Technology, Huainan, 232001, China.
  • 4 Medical School, Anhui University of Science & Technology, Huainan, 232001, China. txljd2006@126.com.
  • 5 Institute of Environmentally-Friendly Materials and Occupational Health, Anhui University of Science and Technology (Wuhu), Wuhu, 241003, China. txljd2006@126.com.
  • # Contributed equally.
Abstract

Sorafenib acquired drug resistance during the treatment of hepatocellular carcinoma (HCC) reduces the efficacy of the drug. The immune escape effect induced by PD-L1 is largely associated with drug resistance of HCC. However, the regulated mechanism of PD-L1 is unclear. This research aimed to clarify the control mechanism of PD-L1. c-Met was found abnormally highly expressed in Huh-7SR with high PD-L1 expression. In addition, c-Met, as the upstream target molecule of PD-L1, promoted the proliferation and migration of HCC in vitro and in vivo. We also found that c-Met activated the MAPK signaling pathway and the downstream NF-κBp65 transcription factor, which interacts with the proximal region of the PD-L1 promoter to promote PD-L1 expression. In conclusion, c-Met regulates the transcription of PD-L1 through the MAPK/NF-κBp65 pathway, thereby promoting the progress of HCC. The role of c-Met and PD-L1 in HCC needs to be further studied, but it is a potential target for the treatment of HCC. KEY MESSAGES: In the study, it was found that c-Met is also abnormally highly expressed in Huh-7SR with high PD-L1 expression and can promote the development of HCC in vitro and in vivo. PD-L1 and c-Met expression levels are positively correlated. In the follow-up mechanism study, we found that c-Met activated the MAPK signaling pathway and subsequently activated the downstream NF-κBp65 transcription factor, which interacts with the proximal region of the PD-L1 promoter to promote PD-L1 expression. Our study found that c-Met regulates the transcription of PD-L1 through the MAPK/NF-κBp65 pathway, thereby promoting the progress of HCC.

Keywords

MAPK/NF-κBp65 pathway; PD-L1; c-Met.

Figures
Products