支架蛋白IQGAP1与肿瘤研究现状

Relationship of scaffold protein IQGAP1 and biological behavior of tumor

目的总结支架蛋白IQGAP1与肿瘤的研究进展,探讨其在恶性肿瘤迁移、侵袭和增殖方面的作用。方法应用PubMed和CNKI期刊全文数据库检索系统,以"支架蛋白1和肿瘤"为关键词,检索2000-01-2013-07相关文献,纳入标准:1)支架蛋白IQGAP1的特性和功能;2)支架蛋白IQGAP1在肿瘤组织中的表达;3)针对IQGAP1为靶点的肿瘤细胞相关实验研究。根据纳入标准,符合分析的文献35篇。结果 IQGAP1作为一种细胞骨架蛋白,在肿瘤细胞的运动和增殖等方面的作用引起越来越多的重视。首先IQGAP1可激活Rac1/CDC42信号通路,促使细胞形成侵袭性伪足;与肌动蛋白形成多聚体,引导细胞定向运动;减少正常细胞连接的E-cadherin复合体形成,降低细胞间的黏附力;加速细胞外基质(extracellular cell matrix,ECM)降解增强肿瘤细胞的侵袭能力。同时,IQGAP1还可激活MAPK/Raf/MEK/ERK信号传导通路,与β-catenin结合控制Wnt通路,后两者是促进细胞增殖的重要通路;与VEGF形成复合体,提高血管内皮细胞的运动和增殖能力,促进肿瘤血管的增生。IQGAP1在结肠癌、乳腺癌、肺癌、前列腺癌和卵巢癌等组织中表达明显增高,并与肿瘤复发、远处转移和患者生存时间密切相关;IQGAP1胞膜分布预示肿瘤的复发与分化,在侵袭性强、分化低的肿瘤IQGAP1更多分布于细胞外周;其通过改变上皮细胞的极性参与幽门螺杆菌导致胃肠道肿瘤的发病机制。结论支架蛋白IQGAP1在肿瘤细胞的运动、侵袭和增殖等生物学行为中发挥重要功能,在肿瘤组织中的表达和定位与肿瘤复发、转移和预后判断密切相关。IQGAP1在肿瘤的基础和临床研究中具有广阔的前景。

OBJECTIVE To summarize progress in the study of IQGAP1 associated with tumor,and explore the role of IOGAP1 in tumor cells migration,invasion and proliferation.METHODS Related publications were searched with＂IQGAP1,tumor＂as key words between 2000 and 2013in Pubmed and CNKI.Inclusion criterion：1）The characters and functions of IQGAP1;2）The expression of IQGAP1 in tumor tissues;3）The experimental research about targeting IQGAP1 in tumor cells.Finally,35 articles were collected.RESULTS As a scaffold protein,the role of IQGAP1 in the movement and proliferation of tumor cells has drawn more and more attention.At first,IQGAP1 could activate Rac1/CDC42 signaling pathways,promoting the formation of invasive pseudopodia;it could form polymer with actin,leading cells move directionally;IQGAP1could prevent formation of E-cadherin complex,destroy intercellular adhesion;IQGAP1accelerates the degradation of ECM to increase tumor cells invasion.IQGAP1 also could activate MAPK/Raf/MEK/ERK signaling pathway and Wnt pathway withβ-catenin,which are important pathways to promote cell proliferation;Combining with VEGF,IQGAP1 could improve the movement and proliferation of vascular endothelial cells and tumor angiogenesis could be advanced.IQGAP1 expression in colon cancer,breast cancer,lung cancer,prostate cancer and ovarian cancer increased obviously;Tumor recurrence,distant metastasis and patients＇ survival time are closely related to IQGAP1;The intracellular location of IQGAP1 is related to tumor recurrence and differentiation.IQGAP1 was observed to distribute in plasma in strong invasive and poorly differentiated tumors.IQGAP1 was involved in the gastrointestinal tumors pathogenesis caused by helicobacter pylori bacteria by changing the polarity of epithelial cells.CONCLUSIONS IQGAP1 plays essential role in migration and proliferation of tumor cells and aberrant expressions in multiple tumors were described closely associated with development,metastasis and prognosis of tumors.IQGAP1 shows broad prospects in the basic and clinical studies of tumors.