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目的:对Vav1的结构、功能及其与肿瘤相关性的研究进展进行概述。方法:应用PubMed及CNKI期刊全文数据库检索系统,以“Vav1和肿瘤”为关键词,检索2000-2012的相关文献177篇,全部为英文文献,国内鲜见相关报道。纳入标准:1)Vav1的结构和生物学功能;2)Vav1与成纤维细胞的转化;3)Vav1在肿瘤中的异常表达及其与肿瘤的相关性。根据纳入标准,符合分析的文献17篇。结果:Vav1蛋白具有鸟苷酸交换因子(GEF)活性,其结构由CH、DH、PH、SH2和SH3等多个结构域组成。Vav1特异于造血系统表达,在T淋巴细胞激活和发育过程中起着关键作用。Vav1以GEF依赖或GEF非依赖的机制诱导成纤维细胞的转化。Vav1在各种实体瘤中异常表达并扮演着促进肿瘤生长或侵袭的角色。研究表明,Vav1在肿瘤中的异常表达与转录因子c-Myb及Vav1基因启动子的去甲基化有关。结论:Vav1在肿瘤中异常表达并且促进肿瘤的生长和侵袭,可以作为肿瘤分子靶向治疗的潜在靶点。
OBJECTIVE: To summarize the research progress on the structure and function of Vav1 and its relation with tumor. Methods: Using PubMed and CNKI full-text database retrieval system, with “Vav1 and tumor” as the key words, 177 articles of 2000-2012 were searched, all of them were in English and few were reported in China. Inclusion criteria: 1) the structure and biological function of Vav1; 2) the transformation of Vav1 into fibroblasts; and 3) the abnormal expression of Vav1 in tumors and its association with tumors. According to the inclusion criteria, 17 articles were analyzed. Results: The Vav1 protein has guanylate exchange factor (GEF) activity and its structure consists of multiple domains of CH, DH, PH, SH2 and SH3. Vav1 is specific for hematopoietic system expression and plays a key role in T lymphocyte activation and development. Vav1 induces fibroblast transformation in a GEF-dependent or GEF-independent mechanism. Vav1 is abnormally expressed in various solid tumors and plays a role in promoting tumor growth or invasion. Studies have shown that the abnormal expression of Vav1 in tumors is related to the demethylation of the c-Myb transcription factors and the Vav1 gene promoter. Conclusion: The abnormal expression of Vav1 in tumor and the promotion of tumor growth and invasion can be used as potential targets for tumor molecular targeted therapy.