Wild-type KRAS inhibits the migration and invasion of pancreatic cancer through the Wnt/β-catenin pathway

Kirsten rat sarcoma virus (KRAS) mutation is considered to be the event that leads to the initiation of pancreatic ductal adenocarcinoma (PDAC), the mutation frequency of the KRAS gene in PDAC is 90–95%. Studies have shown that wild-type KRAS (KRAS(WT)) has a survival advantage in PDAC and can antagonize the effect of mutated KRAS G12D (KRAS(G12D)), leading to a low cell transformation efficiency. The present study focused on the differences in biological behavior between KRAS(WT) and KRAS(G12D) and explored the mechanism in pancreatic cancer. Overexpressed KRAS(WT) and KRAS(G12D) was transfected into cells through lentiviral transfection. The differences and mechanisms were explored using cell counting kit-8 (CCK-8), clone formation, wound healing and Transwell assays, as well as western blotting, immunohistochemistry and tumor formation in nude mice. In vitro, the proliferation of KRAS(WT) group was reduced compared with PANC-1 group, while the proliferation of KRAS(G12D) group was not significantly changed. In vivo, the proliferation of KRAS(WT) group was reduced and that of KRAS(G12D) group was enhanced compared with that in the PANC-1 group. The invasion and migration of KRAS(WT) group were decreased, while the invasion and migration of KRAS(G12D) group were increased. Western blotting showed that the expression of E-cadherin, α-E-catenin, MMP-3, MMP-9, STAT3 and phosphorylated STAT3 in KRAS(WT) group was increased, while no significant difference was observed in KRAS(G12D) group. The results of immunohistochemistry were consistent with those of western blotting. KRAS(WT) group can inhibit the proliferation of pancreatic cancer in vitro and in vivo, while KRAS(G12D) group can significantly promote proliferation in vivo, but not significantly in vitro. Wild-type KRAS may inhibit the invasion and migration of pancreatic cancer through the Wnt/β-catenin pathway.