转移复发是制约肝癌预后的关键因素，筛选肝癌转移相关基因、探明其分子机制是进行肝癌早期预测和干预的关键。本课题组前期工作已证实MST4可增强肝癌细胞侵袭转移能力。本项目预实验发现MST4可能与ERM家族蛋白ezrin有相互作用，故本项目将进一步通过体外、体内功能研究及基因突变技术验证二者的相互作用，明确二者在肝癌转移中的作用。进而应用免疫共沉淀、蛋白质谱技术和信号通路数据库研究分析寻找MST4-ERM下游靶蛋白，并通过体内外功能实验对其功能进行验证，阐明MST4在肝癌转移中的信号通路和作用机制。同时分别回顾性、前瞻性研究MST4、ERM及下游靶蛋白在肝癌患者肿瘤组织中的表达水平及其与肝癌转移复发及病人预后间的关系，构建肝癌转移预测模型。通过上述研究，阐明MST4调控肝癌转移潜能的分子机制及其进行肝细胞癌转移预测的可行性。

Metastatic recurrence of hepatocellular carcinoma(HCC) is a key limiting factor of patients’ prognosis. In order to improve the curative effect of HCC, it becomes more and more crucial to select driven genes related to metastases, reveal its molecular mechanism and find effective approaches of prevention and treatment. In the preliminary work of this group, MST4 had been approved to enhance the potential of metastases in HCC cell lines, in which feasible mechanism is that MST4 could regulate the modeling of cytoskeletion via interacting with ezrin(belongs to ERM family). Accordingly, this project is designed to demonstrate the detailed signaling pathway and molecular mechanism for the purpose of making MST4 function clear and confirm both its direct physical interaction with ezrin and influention on HCC metastasis utilizing genomic and proteomic methods, as an example, gene mutation, co-immunoprecipitation(CO-IP) and mass spectrometry(MS). Meanwhile, functional assays will be performed in vivo and in vitro. Aimed to discover the axis of MST4-ERM, the proteins which could possess the interaction with active status or inactive status of ezrin all will be investigated by IP-MS/Ms and analized by bioinformatic programme. A series of experiments will be done on Candidated protein for validation and conduction of the axis of MST4-ERM. Furthermore, applied of prospective and retrospective study on the expression level of the axis of MST4-ERM in a large scale of HCC tissues, it is intended to uncover the relationship between the axis and clinical index including metastatic recurrence and patients’ prognosis. And a prediction model about MST4-ERM axis of HCC will be constructed under this condition. After illuminating the molecular mechanism of MST modulating HCC metastasis, it will supply a slice of approvement that it is promissing to break new ground for predict the metastasis of HCC by the expression level of MST4.