1. Academic Validation
  2. PD-L1/PD-L1 signalling promotes colorectal cancer cell migration ability through RAS/MEK/ERK

PD-L1/PD-L1 signalling promotes colorectal cancer cell migration ability through RAS/MEK/ERK

  • Clin Exp Pharmacol Physiol. 2022 Sep 1. doi: 10.1111/1440-1681.13717.
Yihui Cao  # 1 Weiye Liang  # 2 Lian Fang  # 2 Ming-Kai Liu 2 Jia Zuo 2 Ying-Long Peng 2 Jia-Jie Shan 2 Rui-Xia Sun 3 Jie Zhao 2 Jian Wang 1 2 3
Affiliations

Affiliations

  • 1 School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China.
  • 2 Department of Neurobiology, School of Medicine, South China University of Technology, Guangzhou, China.
  • 3 Bioscience Laboratory, BIOS bioscience and Technology Limited Company, Guangzhou, China.
  • # Contributed equally.
Abstract

Programmed death ligand 1 (PD-L1) is widely known as an immune checkpoint, and immunotherapy through the inhibition of checkpoint molecules has become an important component in the successful treatment of tumours via programmed death 1 (PD-1)/PD-L1 signalling pathways. However, its biological functions and expression profile in colorectal Cancer (CRC) are elusive. We previously found that PD-L1 can bind to PD-L1 and cause cell detachment. However, the detailed molecular mechanisms of how PD-L1 binds to PD-L1 and how it transmits signals to the cell remain unclear. In this study, we disclosed that PD-L1 expression was dramatically upregulated in CRC compared to normal tissues. Ectopic expression of PD-L1 inhibits cell adhesive capacity and promotes cell migration in CRC cell lines, while silencing PD-L1 had the opposite effects and suppressed invasion and proliferation. Mechanistically, PD-L1 was found to promote epithelial-mesenchymal transition (EMT) through the ERK signalling molecule pathway and interacted with the 1-86 aa fragment of KRAS to transduce signals. Collectively, our study demonstrated the role of PD-L1 after binding to PD-L1 in CRC, thereby providing a new theoretical basis for further improving immunotherapy with anti-PD-L1 Antibodies.

Keywords

ERK; KRAS; PD-L1; cell adhesion; colorectal cancer (CRC); migration.

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