Cilia（微纤毛）是一种微管结构亚细胞器，参与多种生物学功能。但Cilia在肿瘤发生发展过程中的作用目前还不甚清楚。 在前期研究工作中，我们发现多种临床肿瘤样本和肿瘤细胞系中都出现Cilia丢失。体外转化实验也证实从正常细胞转化成肿瘤细胞过程中Cilia出现丢失，而且Cilia丢失程度与细胞转化程度呈正相关。通过Microarray分析，我们发现甲羟戊酸途径在Cilia丢失的细胞中显著活化。在本研究中，我们拟利用细胞生物学、分子生物学、动物模型等技术方法，进一步研究Cilia丢失活化甲羟戊酸代谢途径的分子机制，以及甲羟戊酸代谢途径改变对肿瘤发生的影响，探索甲羟戊酸途径的抑制剂-他汀类药物对Cilia丢失相关肿瘤的治疗作用。我们希望通过本项目的研究，揭示Cilia在肿瘤发生发展中的重要作用及机制，从肿瘤代谢的角度为肿瘤的治疗提供新的靶点。

Primary cilia, a microtubule-based organelle, plays a very important role in various biological events. However, the role of cilia in tumorigenesis remains largely unexplored. In our preliminary study, we have found cilia loss in different cancer cell lines as well as primary tumors compared to their normal counterparts. Interestingly, loss of cilia was also observed during cell transformation induced by oncogenic E1A-Ras genes, and the degree of cell transformation was tightly correlated with the extent of cilia loss. Moreover, microarray analysis revealed that mevalonate signaling pathway was activated in the cells which lost cilia. In this study, we will investigate the mechanism of cilia loss during cell transformation and the effects of mevalonate pathway on the tumorigenecity with the combination of techenologies of cell biology, molecular biology and animal model. At the same time,we will explore the therapeutic potential effects of statin, an inhibitor of the mevalonate pathway, on the cilia loss-related cancers.