肺癌由于不易早期发现，致使 5年生存率仅5-15%，成为死亡率最高的恶性肿瘤之一。肺癌肿瘤干细胞不仅是肿瘤发生和转移的起因，而且是导致肿瘤治疗抵抗的主要原因。临床研究发现癌蛋白MUC1在70%以上的肺癌中异常高表达。申请人前期利用细胞系研究结果显示MUC1的高表达与肺癌细胞的成瘤和转移性增强等肿瘤干细胞特征密切相关，本项目拟在此基础上，利用MUC1表达差异细胞系和肺癌病例临床样本, 从细胞水平和患者组织水平系统研究MUC1表达水平及表达模式与肺癌细胞干性及患者生存率的相关性；揭示MUC1高表达与肺癌干细胞的关系及在肺癌早期发生和转移中的作用； 阐明MUC1高表达导致肺癌早期发生和转移的分子机制。最终为肺癌的早期诊断、治疗及预后提供新的分子标志物，为以MUC1为靶点的肿瘤治疗药物的研发提供实验基础和理论依据。

Lung cancer is the leading cause of cancer mortality in the world. Due to metastasis in early stage, the 5-year survival rate for patients is only 5-15%. Cancer stem cells account for not only tumor initiation, development and metastasis, but also the ineffectiveness of cancer therapies. MUC1 is an oncoprotein that aberrantly overexpressed in 70% of lung cancer. Our preliminary data indicated that MUC1 induces tumorigenesis and metastasis in lung cancer cell line. A better understanding of the mechanisms underlying such MUC1 activation will not only offer new insight into early stage tumorigenesis but also enable the development of strategies to block MUC1 function for cancer therapeutics. The proposed work will extend our study 1) to investigate the association of MUC1 and cancer stem cell; 2) to elucidate the mechanism of how MUC1 effects on cancer stem cell and thereby promotes tumorigenesis and metastasis in lung cancer.