程序性细胞死亡分子10调控EphB4信号通路促进胶质母细胞瘤迁移和侵袭的作用及其机制

目的:探讨程序性细胞死亡分子10(PDCD10)调控胶质母细胞瘤(GBM)迁移和侵袭的作用与机制。方法:采用慢病毒转染GBM细胞系(U251和U373)构建稳定转染的PDCD10过表达(oxPDCD10)或沉默(shPDCD10)的GBM细胞系。分别采用划痕实验和Transwell实验检测细胞迁移和侵袭。蛋白质印迹法(...

Programmed cell death molecule 10 mediated EphB4 signaling pathway in promoting glioblastoma cell migration and invasion

Objective To investigate the role and mechanism of programmed cell death molecule 10(PDCD10)in regulating glioblastoma(GBM)migration and invasion.Methods Stable knockdown and overexpression of PDCD10 in GBM cell lines(U251 and U373)were established by transfection with lentivirus containing shPDCD10,oxPDCD10 and corresponding controls,respectively.Cell migration and invasion were examined by scratch assay and Transwell assay,respectively.Western blotting was used to detect the expression of PDCD10,EphB4,extracellular-regulated kinase(Erk)1/2 and pErk1/2.A compensation assay was achieved by the silence of EphB4(siEphB4)in oxPDCD10 GBM cells.Results The expression of PDCD10 and EphB4 in GBM patients was higher than in controls and displayed a positive correlation(203.4±17.9 vs.100.0±12.4,t=8.225,P<0.05).Downregulation of PDCD10 decreased the migration and invasion of GBM cell lines,while overexpression of PDCD10 significantly accelerated the migration(152.8±27.3 vs.97.6±16.4,P<0.05)and invasion(152.9±11.8 vs.89.4±16.6,P<0.05)ability of GBM cell lines(P<0.05).Moreover,shPDCD10caused a decrease in the expression of EphB4 and p-Erk1/2,while oxPDCD10 induced a higher expression of EphB4.In addition,transfection of siEphB4 in oxPDCD10 GBM cells dominantly attenuated the increase of migration and invasion(P<0.05).Conclusion PDCD10 in GBM can activate the Erk1/2 signaling pathway and promote GBM migration and invasion in vitro by regulating the EphB4 expression.