Department of Clinical Laboratory, Taizhou Second People's Hospital, Taizhou, Jiangsu 225599, P.R. China.
Department of Gastroenterology, Taizhou Second People's Hospital, Taizhou, Jiangsu 225599, P.R. China.
Oncol Rep. 2017 Oct;38(4):2325-2334. doi: 10.3892/or.2017.5920. Epub 2017 Aug 24.
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.
表皮生长因子 (EGF) 信号已被证明可诱导多种类型癌细胞发生上皮间质转化 (EMT)。然而，EGF 诱导胃癌 EMT 的分子机制在很大程度上仍不清楚。在本研究中，我们发现人胃癌细胞系 SGC-7901 和 BGC-823 在暴露于 EGF 时经历 EMT 表型变化。EMT 的诱导与侵袭和克隆形成等侵袭性特征一致。此外，EGF 刺激还导致尿激酶型纤溶酶原激活物受体 (uPAR) 的 mRNA 和蛋白水平上调。siRNA 敲低 uPAR 可显著减弱 EGF 诱导的 SGC-7901 和 BGC-823 细胞 EMT 的诱导。此外，EGF 增加 ERK1/2 活性，并用其抑制剂 U0126 阻断 ERK1/2 信号通路，可显著抑制 EGF 诱导的 uPAR 表达和 EMT。总之，本研究表明 EGF 通过激活 EMT 诱导胃癌细胞的侵袭性，涉及 ERK1/2 途径的激活和随后的 uPAR 表达。
