Overall, our study showed that ITGB4 and its phosphorylated form promote cell migration and invasion in pancreatic cancer and that p-ITGB4-Y1510 regulates the downstream MEK1-ERK1/2 signaling cascades.
Further mechanism related studies demonstrated that ERK1/2-ZEB1 pathway-triggered epithelial-mesenchymal transition (EMT) might be responsible for the PIK3R3-induced PC cell migration and invasion.
Inhibiting MEK1/ERK1/2 pathway with sorafenib could improve the cytotoxity of HHT in vitro and in a genetically engineered mouse model of pancreatic cancer.
Also in contrast to HPDE cells, ethanol did not attenuate ERK1/2 phosphorylation in pancreatic cancer cells; however, inhibiting ERK1/2 decreased pancreatic cancer cell invasion.
These in vitro characteristics translated to increased tumor growth in both subcutaneous and orthotopic pancreatic cancer murine models and also led to increased liver metastasis. mTrop2 expression also increased the levels of phosphorylated ERK1/2 mediating cell cycle progression by increasing the levels of cyclin D1 and cyclin E as well as downregulating p27.