肺癌患者主要死于癌细胞转移。研究转移相关基因对肺癌转移机制的阐明、肺癌的预防及治疗具有重要意义。PROM1在多种肿瘤的侵袭转移中发挥重要作用。我们前期研究在世界上首次发现非小细胞肺癌（NSCLC）存在PROM1-S281R突变,导致PROM1蛋白水平上调；同时NSCLC患者PROM1蛋白水平显著高于正常组织且PROM1膜表达阳性是影响NSCLC预后的独立因素。为证实PROM1-S281R突变导致PROM1高表达从而促进NSCLC转移，本课题拟通过过表达PROM1及其S281R突变体、沉默PROM1，体内外观察PROM1-S281R对肺癌细胞转移的影响；利用蛋白质组学及基因表达芯片技术，探索PROM1-S281R对肺癌细胞转移调控机制；在临床标本中应用生物统计分析及免疫组化方法，研究PROM1-S281R突变所影响信号通路的改变与患者生存预后的关系。本课题将为肺癌转移提供新的理论依据。

Most cancer patients die from cancer cell metastasis; however, the molecular mechanism of cancer cell metastasis remains largely unknown. The growth, proliferation, survival, invasion and metastasis of cancer cells in the complicated host microenvironment depend on continuous gene mutations. Therefore, the identification of these mutated genes is of critical importance for the elucidation of the mechanism of cancer cell metastasis and searching for targets for the development of therapies of cancer metastasis. We for the first time in the world discovered a novel PROM1 (841T→G, S281R) point mutation in non-small cell lung carcinoma (NSCLC). We further found that PROM1 (841T→G, S281R) mutation results in increased expression of PROM1 and is closely associated with the progression of NSCLC. However, the role and molecular mechanism of PROM1-S281R mutation in the initation, development and metastais of NSCLC is unclear. Further clinic analyses revealed that membrane expression of PROM1 and lymph lobe metastasis are independent prognostic factors for NSCLC. Based on our previous findings, we speculate that PROM1-S281R mutation leads to upregulation of PROM1 expression, thereby promoting metastasis of NSCLC. In this proposed study, we will investigate the mechanism of PROM1 and its mutation (841T→G, S281R) in the progression and metastasis of NSCLC. By proteosome analysis, we will identify the potential proteins that interact with PROM1, which may be interrupted by PROM1-S281R mutation, and assess the different gene expression signatures between wild type and S281R mutant PROM1 by gene expressing profiling. Our study will elucidate the signaling pathways by which PROM1 S281R mutation promotes the tumorigenesis and metastasis of NSCLC and provide potential targets for the development of molecularly targeted therapy for NSCLC.