Ebp1介导的Akt/HDM2/p53信号通路在ErbB3异常激活引起的肝癌细胞EMT中的作用

ErbB3信号通路的过度激活可提高肝癌细胞的迁移和侵袭性，其作用机制与上皮间质转化（EMT）有关。Ebp1是新发现的ErbB-3胞内结合蛋白，可调控Akt的磷酸化。我们前期研究发现，Ebp1在肝癌组织中的表达量与p53的表达和淋巴转移正相关，且稳定转染Ebp1促进肝癌细胞侵袭转移，并激活Akt的磷酸化。Akt/p53信号通路能够诱导肿瘤细胞发生EMT，因此我们推测Ebp1调控的Akt/ HDM2/p53信号通路可能参与ErbB3异常激活引起的肝癌细胞EMT的发生。本项目拟利用临床肝癌标本、动物模型、肝癌细胞系、分子生物学技术，（1）明确Ebp1参与肝癌细胞发生EMT的可能性；（2）靶向于AKT/HDM2/p53信号通路阐明Ebp1在肝癌细胞发生EMT中的分子机制；（3）探讨ErbB3异常激活引起的肝癌细胞EMT对Ebp1调控的信号网络的依赖性。旨在为肝癌侵袭转移机制提供新的靶点和理论依据。

The over activation of ErbB3 signaling pathway can enhance the migration and invasion of HCC cells, and its mechanism is related to epithelial mesenchymal transition (EMT). Ebpl is a newly discovered intracellular binding protein of ErbB-3, which can regulate the phosphorylation of Akt. We found that the expression of Ebp1 in HCC tissues was positively correlated with the expression of p53 and lymphatic metastasis, Stable transfection of Ebp1 promotes invasion and metastasis of hepatocellular carcinoma cells and activate the phosphorylation of Akt. Akt/p53 signaling pathway can induce tumor cell EMT. Therefore, we hypothesized that the Akt/HDM2/p53 signaling pathway regulated by Ebp1 may be involved in the occurrence of EMT in hepatocellular carcinoma cells induced by abnormal activation of ErbB3. This project intends to use the clinical liver cancer specimens, animal models, hepatocellular carcinoma cell lines, molecular and cellular biology techniques, (1) To clarify the possibility of Ebp1 mediated EMT in hepatocellular carcinoma cells, (2)To elucidate the molecular mechanism of hepatoma cells EMT induced by Ebp1 through the AKT/HDM2/p53 signaling pathway, (3) To investigate the dependence of molecular signaling network regulated by Ebp1 in hepatocellular carcinoma cell EMT induced by abnormal activation of ErbB3. To provide a new target and experimental basis for the mechanism of invasion and metastasis of HCC.