我们新近观察到在宫颈癌组织中WNT2的上调与患者的淋巴结转移和不良预后密切相关；而肿瘤组织中RASSF8基因和蛋白的表达则显著下调并与β-catenin抑制物APC的表达呈正相关。我们推测RASSF8很可能通过调控Wnt/β-catenin通路来抑制宫颈癌的进展和转移。本课题拟首先扩大样本在配对的肿瘤、癌旁和淋巴结组织中检测RASSF8与Wnt通路分子之间的相关性和临床意义；通过建立稳定降低和过表达RASSF8的宫颈癌/正常宫颈上皮细胞株，在体外实验和动物模型中明确RASSF8对细胞增殖和转移的影响，及其与Wnt/β-catenin通路的相关性；并在过表达WNT2细胞株中进一步明确RASSF8的功能以及它们之间相互作用与机制；最后，在上述模型中探讨Wnt通路抑制剂对细胞增殖转移潜能的作用以及RASSF8对该抑制剂药敏的影响。所得的结果可望为寻找宫颈癌治疗新靶点和个体化干预提供新的方向

We recently observed that upregulation of WNT2 in patients with cervical carcinoma was closely related to lymph node metastasis and poor prognosis. RASSF8 gene and protein expression in tumor tissue, however, was significantly reduced and was positively correlated with the expression of ?-catenin inhibitor APC. We speculate that RASSF8 is likely to inhibit progression and metastasis of cervical cancer through the regulation of Wnt/ ?-catenin pathway. This project intends to firstly expand samples in paired tumor, adjacent tissues and lymph nodes, to explore correlation between RASSF8 and Wnt pathway molecules, and it's clinical significance. By establishing stable lower expression and overexpression RASSF8 cervical cancer / normal cervical epithelial cell line, the effects of RASSF8 on cell proliferation and metastasis and its correlation with the Wnt/ ?-catenin pathway, will be cleared in vitro cell experiments and animal models. Further study will clarify the functionality of RASSF8 in overexpressed Wnt2 cervical cancer cell lines, and the interaction mechanisms. Finally, based on above model, we'll explore the metastatic potential role of Wnt pathway inhibitors on cell proliferation and the influence of RASSF8 on Wnt inhibitors susceptibility. The achieved results are expected to provide a new direction for looking for new targets of cervical cancer and individualized intervention.