分子靶向治疗开启了肿瘤治疗的新纪元，索拉非尼的临床应用只是肝癌系统治疗所迈出的第一步。开展肝癌发生发展机制的深入研究，寻找并鉴定新型分子靶标对改善肝癌患者的预后生存具有重要意义。在前期工作中，我们发现重组CADM1分子使肝癌细胞生长停滞于G0/G1期，并伴随Rb分子表达明显上调。本课题将系统研究CADM1分子在肝癌发生发展中的作用及其分子机制。应用分子克隆及基因转染等方法，通过体内、外两个层面过表达、沉默CADM1和Rb，观察转染前后细胞增殖、凋亡、侵袭和迁移等生物学行为的改变，检测细胞周期Rb-E2F信号通路相关分子的变化；并分别从转录和转录后水平探讨CADM1调控Rb表达的分子机制。鉴于Rb分子在细胞周期调控中的核心作用，深入研究CADM1在肝癌中的作用并确立CADM1-Rb-E2F通路或可以为肝癌发生发展机制的阐明和分子靶向治疗措施的优化提供新的方向和思路，从而提高肝癌的治疗水平。

Molecular targeted therapies represent the dawn of a new era in the management of cancer patients. The advent of sorafenib constitutes a first step in the complex management of hepatocellular carcinoma(HCC), which should be complemented with other molecular approaches. It is of great significance for improving the prognosis of patients with HCC by carrying out in-depth study of the mechanism of the development, finding and identifying new molecular targets of this disease. In our previous work, ectopic expression of CADM1 suppressed HCC cells growth and induced G0/G1 arrest accompanied with obvious upregulation of Rb protein. Our project will systematically explore the roles and molecular mechanisms of CADM1 in the initiation and progression of HCC. By applying the techniques of molecular cloning and transfection, our team will observe the effects of CADM1 and Rb on the cell growth, apoptosis, invasion and migration in HCC through gain of function and loss of function in vivo and in vitro, detect the alterations of related molecules in Rb-E2F signal pathway, and explore the molecular mechanism of CADM1 regulation of Rb expression from the transcriptional and posttranscriptional level. In view of the fact that Rb protein plays a fundamental role in cell cycle control, to explore in-depth the roles of CADM1 in HCC and establishment of CADM1-Rb-E2F pathway may provide new directions and ideas to clarify the molecular mechanisms for the initiation and progression of HCC and to optimize the ways of molecular targeted therapy.