EGF-induced urokinase plasminogen activator receptor promotes epithelial to mesenchymal transition in human gastric cancer cells.

ABSTRACT

Epidermal growth factor (EGF) signaling has been shown to induce epithelial to mesenchymal transition (EMT) in many types of cancer cells. However, the molecular mechanism of EGF-induced EMT in gastric cancer remains largely unknown. In the present study, we found that human gastric cancer cell lines SGC-7901 and BGC-823 underwent EMT phenotypic changes upon exposure to EGF. The induction of EMT was consistent with aggressive characteristics such as increased cell migration, invasion and clonogenic growth. Additionally, EGF stimulation also led to the upregulation of urokinase plasminogen activator receptor (uPAR) both at mRNA and protein levels. Knockdown of uPAR by siRNA significantly attenuated EMT induction by EGF in SGC-7901 and BGC-823 cells. Furthermore, EGF increased ERK1/2 activity and blocking ERK1/2 signaling with its inhibitor, U0126, markedly inhibited EGF-induced uPAR expression and consequently EMT. Collectively, the present study demonstrated that EGF induced aggressiveness of gastric cancer cells by activating EMT, which involved the activation of the ERK1/2 pathway and, subsequently, uPAR expression.