抑癌基因R-spondin2通过JNK通路抑制肝癌细胞增殖及转移的作用机制

R-spondin2是血小板1型重复蛋白的超家族成员之一，既往研究表明该家族成员具有激活Wnt/β-catenin信号通路促进肿瘤增殖的作用。而本课题组前期研究表明，R-spondin2在癌旁组织中高表达，当肝癌细胞中过表达R-spondin2基因后能够显著抑制癌细胞增殖并诱导细胞凋亡。通过进一步的表达谱芯片筛选及western-blot验证表明过表达R-spondin2基因后JNK信号通路被异常激活。因此本课题组拟在前期研究基础上通过进一步扩大临床样本量并且使用CCK8、划痕、trans-well、流式、质谱分析等方法对R-spondin2基因诱导细胞凋亡、抑制肝癌增殖及转移的机制进行研究。目的在于明确R-spondin2基因抑制肝癌细胞增殖及诱导细胞凋亡的机制，并为R-spondin2的临床医学应用提供依据。

R-spondin2 is the member of a superfamily of thrombospondin type 1 repeat(TSR-1)-containing proteins. As an activator of Wnt/β-catenin pathway R-spondins have been reported by many researchers recently. Our recent work showed that R-spondin2 was down-regulated or lost in hepatocellular cancer (HCC) tissues, while it was highly expressed in adjacent normal liver tissues. Overexpressing R-spondin2 could inhibit proliferation and induce apoptosis in HCC cells. After microarray screening and western-blot confirming, JNK pathway was found to be activated. The project will employ CCK8, scratch adhesion test, trans-well, flow-cytometry, and HPLC-MS to investigate the role of R-spondin2 gene in the proliferation，apoptosis and metastasis of HCC, aim to confirm the function of R-spondin2 in inhibiting HCC cells proliferation and inducing cells apoptosis.