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目的:总结国内外关于MEKK1在肿瘤MAPK信号通路中的调控作用,及其对肿瘤转移、细胞迁移和运动影响的研究进展。方法:应用Medline及CNKI期刊全文数据库检索系统,以“MEKK1、MAPK信号转导和肿瘤”为关键词,检索1992-01-2008-01的相关文献,共检索到英文文献4046篇和中文文献2篇。纳入标准:1)MEKK1的来源和分子结构特征;2)MEKK1与肿瘤相关的MAPK信号通路及其他信号通路的关系;3)MEKK1与AP1的关系;4)MEKK1与肿瘤细胞凋亡的关系;5)MEKK1与肿瘤细胞迁移和运动的关系。根据纳入标准,精选55篇文献,最后纳入分析21篇文献。结果:MEKK1是MAPK信号传导通路中的重要结点,也是MAPK通路与其他信号通路的结点。MEKK1具有广泛的生物学功能,如调控NFκB和AP1,影响细胞的存活和凋亡,并且与肿瘤细胞的侵袭、迁移和运动密切相关。结论:MEKK1是抗肿瘤药物研究的潜在靶点,虽然目前还没有MEKK1的抑制剂上市,但可通过研究疾病状态下与MEKK1过表达有关的细胞功能来开发MEKK1抑制剂。
OBJECTIVE: To summarize the regulatory role of MEKK1 in MAPK signaling pathway in tumor and its impact on tumor metastasis, cell migration and exercise. Methods: Using the Medline and CNKI journal full-text database retrieval system and the key words of “MEKK1, MAPK signal transduction and tumor”, we searched the relevant literature from January 1992 to January 2008 with 4046 English articles and Chinese 2 articles. Inclusion criteria: 1) the origin and molecular structure of MEKK1; 2) the relationship between MEKK1 and tumor-associated MAPK signaling and other signaling pathways; 3) the relationship between MEKK1 and AP1; 4) the relationship between MEKK1 and tumor cell apoptosis; 5 Relationship between MEKK1 and Tumor Cell Migration and Exercise. According to the inclusion criteria, 55 articles were selected and finally 21 articles were analyzed. Results: MEKK1 is an important node in MAPK signal transduction pathway and a junction between MAPK pathway and other signaling pathways. MEKK1 has a wide range of biological functions, such as regulating NFκB and AP1, affecting cell survival and apoptosis, and is closely related to tumor cell invasion, migration and movement. Conclusions: MEKK1 is a potential target for anticancer drug discovery. Although no inhibitors of MEKK1 are currently available, MEKK1 inhibitors could be developed by studying the cellular functions associated with MEKK1 overexpression in disease states.