肺癌是全球致死率最高的恶性肿瘤之一。肺癌干细胞(LCSC)的存在是肺癌高复发转移的主要原因。人类着色性干皮病C组蛋白(XPC)的缺失或突变与肺癌的预后不良正相关。我们发现，下调XPC能促进CD133-肺癌细胞向CD133+转化，增强其致瘤能力；下调XPC还能增加上皮间皮转化关键蛋白Snail的表达。鉴于Snail在促进癌细胞干细胞化中的作用，推测下调XPC可通过增加Snail表达，促进非LCSC向LCSC转化，导致肺癌复发转移。本研究利用已建立的Tet-on和IPTG双调控XPC和Snail表达的稳定肺癌细胞株，体内外实验检测XPC和/或Snail对肺癌细胞干细胞化及LCSC数量、致瘤性和转移能力的影响；采用基因芯片、蛋白质组、染色质免疫共沉淀及色谱分析等方法，研究XPC调控Snail以及XPC/Snail信号调控LCSC亚群的分子机制，为靶向减少LCSC提高肺癌治疗水平提供理论依据。

Lung cancer is the leading cause of cancer-related deaths in the world. Lung cancer stem cells (LCSC) are the major reason for tumor relapse and metastasis which causes lung cancer patients’ mortality. Xeroderma pigmentosum group C (XPC) is a DNA repair factor mainly involving in the nucleotide excision repair pathway. The low XPC expression level in human lung adenocarcinomas is correlated with a poor outcome of patients, indicating that XPC may play a critical role in suppressing lung cancer progression. Our lab has demonstrated that XPC knockdown is able to increase the abundance of cancer stem cells (CSCs) defined as CD133+ in lung cancer cell lines, and to promote the generation of CD133+ cells from CD133- cell population. Furthermore, our preliminary study revealed that XPC is capable of repressing the expression of epithelial-to-mesenchymal transition (EMT) inducer Snail. Therefore, we hypothesize that XPC depletion in lung cancers promotes non-CSC-to-CSC conversion through enhancing the expression of Snail. The expanded CSC pool is responsible for the enhanced tumorigenic and metastatic potential of lung cancers characterized with low XPC expression. A series of in vitro and in vivo experiments are proposed to test our hypothesis. The elucidation of the significance of XPC in the regulation of the CSC population represents an opportunity to eradicate CSCs and improve the survival of lung cancer patients.