微管调控蛋白CDK5RAP2在口腔鳞状细胞癌转移中的作用及其机制

微管调控蛋白CDK5RAP2对细胞迁移和侵袭有重要的作用，但其在口腔鳞状细胞癌中的作用尚无报道。根据预实验结果，我们提出“CDK5RAP2的表达受Wnt/β-catenin信号通路调控，在口腔鳞状细胞癌中，高表达的CDK5RAP2通过影响细胞有丝分裂时期纺锤体角度调控细胞的对称分裂，促进口腔癌细胞的增殖、迁移、侵袭和干细胞活性，起到促进肿瘤发生发展作用”的科学假说。本项目拟在口腔鳞癌患者组织和细胞系中证实CDK5RAP2的表达变化；通过工具药、敲低或过表达等方法，明确CDK5RAP2对肿瘤细胞的增殖、迁移、侵袭和干细胞活性等生物学行为的作用；揭示Wnt/β-catenin信号通路对CDK5RAP2表达的调控；明确CDK5RAP2对有丝分裂对称性的调控。本研究不仅有助于阐明CDK5RAP2在口腔鳞状细胞癌中的作用及机制，也为以CDK5RAP2为靶点，评估、监测和治疗口腔鳞状细胞癌提供新思路。

The microtubule regulatory protein CDK5RAP2 plays an important role in cell migration and invasion. However, its mechanism in oral squamous cell carcinoma (OSCC) has remained unknown. We proposed that the expression of CDK5RAP2 is regulated by Wnt/β-catenin signaling pathway. High expression of CDK5RAP2 in OSCC affects tumor cell symmetric division through regulating spindle orientation in mitosis. The high expression of CDK5RAP2 promotes the cell proliferation, migration, invasion and stemness in OSCC. We aimed to determine the expression level of CDK5RAP2 in both OSCC tissues and cell lines. Through drug treatment, knock down or overexpression, we will investigate the function of CDK5RAP2 in tumor cell proliferation, migration, invasion and stemness. Moreover, we will confirm the regulation of CDK5RAP2 expression via Wnt/β-catenin signaling pathway and reveal the molecular mechanism of CDK5RAP2 in regulating symmetric cell division in mitosis. This study will not only provide new insights in the function and molecular mechanism of CDK5RAP2 in OSCC, but also suggest novel potential target for evaluation, monitor and treatment of OSCC.