Dou Ning, Chen Jingde, Yu Shijun, Gao Yong, Li Yandong
Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine Shanghai 200120, China.
Department of Oncology, Shanghai East Hospital, Tongji University School of MedicineShanghai 200120, China; Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of MedicineShanghai 200120, China.
Am J Cancer Res. 2016 Nov 1;6(11):2641-2650. eCollection 2016.
RasGAP SH3-domain-Binding Protein 1 (G3BP1) has been implicated in cell growth, migration, and metastasis of some cancers, yet its function in hepatocellular carcinoma (HCC) remains to be explored. In the present study, we reported that G3BP1 was upregulated in HCC tissues compared with adjacent non-cancerous liver tissues both in mRNA and protein levels, and its high expression was significantly correlated with poor prognosis of HCC patients. Functional analyses demonstrated that forced expression of G3BP1 in HCC cells promoted cell migration, and silenced expression of G3BP1 by RNA interference caused opposite effects. Moreover, G3BP1 knockdown attenuated the distant metastasis capacity of HCC cells through tail vein injection approach in nude mice model. At molecular mechanism, we found G3BP1 knockdown decreased Slug expression, and increased the expression of the epithelial cell marker E-cadherin. Overexpression of Slug could restore the phenotype of G3BP1 silencing induced cell migration inhibition. Together, our data establish G3BP1 as an oncogenic factor involved in the metastasis of HCC and suggest that G3BP1 might serve as a novel predictor for patients' outcome.
RasGAP SH3结构域结合蛋白1(G3BP1)与某些癌症的细胞生长、迁移和转移有关,但其在肝细胞癌(HCC)中的功能仍有待探索。在本研究中,我们报道G3BP1在HCC组织中的mRNA和蛋白质水平均高于相邻的非癌性肝组织,其高表达与HCC患者的不良预后显著相关。功能分析表明,在HCC细胞中强制表达G3BP1可促进细胞迁移,而通过RNA干扰使G3BP1表达沉默则产生相反的效果。此外,在裸鼠模型中,通过尾静脉注射方法,G3BP1敲低减弱了HCC细胞的远处转移能力。在分子机制方面,我们发现G3BP1敲低降低了Slug的表达,并增加了上皮细胞标志物E-钙黏蛋白的表达。Slug的过表达可以恢复G3BP1沉默诱导的细胞迁移抑制表型。总之,我们的数据确定G3BP1是参与HCC转移的致癌因子,并表明G3BP1可能作为患者预后的新预测指标。