Endogenous Pancreatic Cancer Cell PD-1 Activates MET and Induces Epithelial-Mesenchymal Transition to Promote Cancer Progression.

ABSTRACT: We recently demonstrated that immune checkpoint PD-1 was endogenously expressed in pancreatic ductal adenocarcinoma (PDAC) cells. Our data indicated that PD-1 proteins are not exclusive to immune cells and have unrecognized signal transduction cascades intrinsic to cancer cells. Building on this paradigm shift, we sought to further characterize PD-1 expression in PDAC. We utilized a phospho-explorer array to identify pathways upregulated by PD-1 signaling. We discovered PD-1-mediated activation of the proto-oncogene MET in PDAC cells, which was dependent on hepatocyte growth factor (MET ligand) and not secondary to direct protein interaction. We then discovered that the PD-1/MET axis in PDAC cells regulated growth, migration, and invasion. Importantly, the PD-1/MET axis induced epithelial-

SUBMITTER: Harper MM 

PROVIDER: S-EPMC9264908 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature