Shi Shuang, Zhong Dong, Xiao Yao, Wang Bing, Wang Wentao, Zhang Fu'an, Huang Haoyang
Department of Neurosurgery, The 1st Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Experimental Research Center, The 1st Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Oncotarget. 2017 Jun 20;8(25):40922-40934. doi: 10.18632/oncotarget.16733.
Recent studies have shown that increased syndecan-1 (SDC1) expression in human glioma is associated with higher tumor grades and poor prognoses, but its oncogenic functions and the underlying molecular mechanisms remain unknown. Here, we examined SDC1 expression in datasets from The Cancer Genome Atlas and the National Center for Biotechnology Information Gene Expression Omnibus. Elevated SDC1 expression in glioma was closely associated with increases in tumor progression and shorter survival. We also examined SDC1 expression and evaluated the effects of stable SDC1 knockdown in glioma cell lines. SDC1 knockdown attenuated proliferation and invasion by glioma cells and markedly decreased PCNA and MMP-9 mRNA and protein expression. In a xenograft model, SDC1 knockdown suppressed the tumorigenic effects of U87 cells in vivo. SDC1 knockdown decreased phosphorylation of the c-src/FAK complex and its downstream signaling molecules, Erk, Akt and p38 MAPK. These results suggest that SDC1 may be a novel therapeutic target in the treatment of glioma.
最近的研究表明，人胶质瘤中syndecan-1（SDC1）表达增加与更高的肿瘤分级和不良预后相关，但其致癌功能和潜在分子机制仍不清楚。在此，我们检查了来自癌症基因组图谱和美国国立生物技术信息中心基因表达综合数据库的数据集中的SDC1表达。胶质瘤中SDC1表达升高与肿瘤进展增加和生存期缩短密切相关。我们还检查了SDC1表达，并评估了在胶质瘤细胞系中稳定敲低SDC1的效果。敲低SDC1可减弱胶质瘤细胞的增殖和侵袭，并显著降低PCNA和MMP-9的mRNA及蛋白表达。在异种移植模型中，敲低SDC1可在体内抑制U87细胞的致瘤作用。敲低SDC1可降低c-src/FAK复合物及其下游信号分子Erk、Akt和p38 MAPK的磷酸化。这些结果表明，SDC1可能是治疗胶质瘤的一个新的治疗靶点。
