标题：CXCR4 Signaling Induced Epithelial-Mesenchymal Transition by PI3K/AKT and ERK Pathways in Glioblastoma
作者：Lv, Baoyu; Yang, Xiangshan; Lv, Shunzeng; Wang, Lei; Fan, Kaixi; Shi, Ranran; Wang, Fengling; Song, Huishu; Ma, Xiaochen; Tan, Xuefe 更多 作者机构：[Lv, Baoyu; Wang, Fengling; Tan, Xuefen; Xu, Kun] Shandong Canc Hosp & Inst, Dept Oncol, Jinan, Peoples R China.; [Yang, Xiangshan; Lv, Shunzeng; Fe 更多
通讯作者地址：[Zhang, L]Shandong Canc Hosp & Inst, Dept Gynecol Oncol, 440 Jiyan Rd, Jinan 250117, Shandong, Peoples R China.
关键词：CXCR4; EMT; PI3K/AKT; ERK; Glioblastoma
摘要：Stromal cell-derived factor 1 (SDF-1) and its receptor, CXCR4, play an important role in tumor progression. Epithelial-mesenchymal transition (EMT) process is linked to disease pathophysiology. This study aimed to investigate the roles and underlying mechanisms of SDF-1/CXCR4 axis in EMT process of glioblastoma. In the present study, CXCR4 activation and inhibition in U87 were induced with exogenous SDF-1 and with CXCR4 small interfering RNA (siRNA), respectively. CXCR4 downstream signal molecules AKT, ERK, and EMT biomarkers (vementin, snail, N-cadherin, and E-cadherin) were tested using the Western blot. Our results showed that SDF-1 can induce AKT and ERK phosphorylation in a dose-dependent manner, and endogenous CXCR4 can be blocked thoroughly by CXCR4 siRNA in U87. Notably SDF-1 alone treatment can induce the upregulation of vementin, snail, and N-cadherin of U87; besides, the downregulation of E-cadherin also occurred. On the contrary, CXCR4 siRNA significantly prohibited SDF-1-induced AKT and ERK phosphorylation, at the same time, EMT biomarker changes were not observed. Function analysis revealed that CXCR4 siRNA obviously interfered with U87 cell migration and proliferation, according to wound healing assay. In conclusion, this study suggested that EMT process can be triggered by the SDF-1/CXCR4 axis in glioblastoma, and then involved in the tumor cell invasion and proliferation via activation of PI3K/AKT and ERK pathway. Our study lays a new foundation for the treatment of glioblastoma through antagonizing CXCR4.