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目的:总结国内外对尿激酶纤维蛋白溶酶原激活剂(uPAR)信号通路的研究进展。方法:应用PubMed及CHKD期刊全文数据库,以“urokinase plasminogen activatorreceptor、integrins、细胞外基质、黏附作用”等为关键词,检索1999-01-2010-10的相关文献352条。纳入标准:1)uPAR的结构与相关功能的研究;2)细胞外基质与细胞间黏附机制的研究;3)整合素与uPAR相关功能的研究。根据纳入标准符合分析的文献38篇。结果:uPAR信号通路复杂,整合素家族是由α,β亚基经非共价连接形成异二聚体的一类重要的跨膜受体,通过介导uPAR信号传递,激活下游包括Ras-MAPK等在内的多条信号通路,改变肿瘤细胞生物学特性,促使肿瘤浸润和转移。目前,对于两者具体的结合方式尚不清楚。结论:uPAR不仅能与uPA结合,降解细胞外基质,实现远处转移;尚能通过信号通路转导信号,促使肿瘤细胞迁移和增殖。由于整合素家族的存在对于uPAR通路是不可或缺的,若明确两者的结合方式,有望通过干扰两者的结合,达到抑制肿瘤浸润生长与远处转移的目的。
Objective: To summarize the research progress of urokinase plasminogen activator (uPAR) signaling pathway at home and abroad. Methods: By using PubMed and CHKD full - text databases, we searched for 352 articles related to “urokinase plasminogen activator receptor, integrins, extracellular matrix and adhesion” from 1999-01-2010-10. Inclusion criteria: 1) the study of the structure and function of uPAR; 2) the study of the mechanism of extracellular matrix and cell adhesion; and 3) the study of the function of integrin and uPAR. According to the inclusion criteria, 38 articles were analyzed. Results: The uPAR signaling pathway is complex. The integrin family is an important class of transmembrane receptors that form non-covalently linked α, β subunits to form heterodimers. By mediating uPAR signaling, the integrin family activates downstream proteins including Ras-MAPK Etc., a number of signal pathways, changing the biological characteristics of tumor cells, promote tumor invasion and metastasis. At present, the specific combination of the two is not yet clear. CONCLUSION: uPAR can not only combine with uPA to degrade extracellular matrix and achieve distant metastasis, but also transduce signal through signal pathway to promote tumor cell migration and proliferation. Because of the existence of integrin family is essential for uPAR pathway, if the combination of the two is clear, it is expected to interfere with the combination of the two to achieve the purpose of inhibiting tumor infiltration growth and distant metastasis.