我们在前期研究证实，ErbB3胞内结合蛋白Ebpl在肝癌组织和细胞中高表达，其长片段p48促进肝癌细胞的增殖和迁移。Akt/mTOR信号途径在HBx蛋白促进肝癌细胞增殖和侵袭转移过程中起重要作用，而我们前期实验中发现，p48 Ebp1的mRNA表达量与HBV感染相关，且稳定转染p48 Ebp1可使肝癌细胞pAkt表达增多。由此我们推测p48 Ebp1可能是新的HBx相关蛋白，影响HBx介导的Akt/mTOR信号途径。本项目进一步检测HBV感染肝癌组织中HBx表达量和Ebp1的表达，探讨HBx表达量与Ebp1及p48 Ebp1是否存在相关性；观察p48 Ebp1高表达或沉默对HBx促进肝癌细胞增殖和侵袭转移的影响及Akt/mTOR信号途径级联信号分子的变化，旨在获得p48 Ebp1参与HBx调控Akt/mTOR信号途径的可靠证据。为丰富HBx在肝癌细胞增殖和侵袭转移中的作用机制提供新的靶点。

Our Previous study has demonstrated that Ebp1 was highly expressed in liver cancer tissues and cells, and the up-regulated p48 Ebp1 promote the proliferation and migration ability of HepG2 cells.Ebpl is a novel ErbB-3 binding protein which has two isoforms, p42 and p48. Hepatitis B virus X protein (HBx) is involved in growth and migration of hepatoma cells through Akt/mTOR signaling pathway. Furthermore, Our recent study shows that Ebp1 mRNA expression of p48 Ebp1 related to HBV infection, and the up-regulated p48 Ebp1 increases the proliferation of glioma cells by Akt phosphorylation. These results suggest that p48 Ebp1 might be involved Akt/mTOR signaling pathway mediated by HBx induced proliferation, invasion and metastasis of liver cancer. We will further evaluate the expression level of HBx and Ebp1 in the liver tissue and cells infected by HBV and investigate the relationship between HBx and Ebp1. In addition, we will determine the effects of HBx on the p48 Ebp1 mediated proliferation, invasion and metastasis of liver cancer cells by using p48 Ebp1 overexpression or knockdown hepatoma carcinoma cell. We will also study whether p48 Ebp1 is involved in HBx mediated Akt/mTOR signaling pathway.This study will reveal the role of p48 Ebp1 on the HBV induced liver cancer progression and metastasis, and provide potentail therapeutic target for hepatocellular carcinoma.