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

Abstract

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.