P21 activated kinase 4 binds translation elongation factor eEF1A1 to promote gastric cancer cell migration and invasion
P21 activated kinase 4 binds translation elongation factor eEF1A1 to promote gastric cancer cell migration and invasion
复制标题
P21激活激酶4结合翻译延伸因子eEF1A1促进胃癌细胞迁移和侵袭
DOI：
10.3892/or.2017.5543
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发表时间：
2017-05-01
期刊：
影响因子：
4.2
通讯作者：
Li, Feng
中科院分区：
文献类型：
--
作者：
Li, Xiang;Li, Jiabin;Li, Feng
P21活化激酶4（PAK 4）作为Cdc 42的效应子，在调节细胞骨架的组装过程中发挥重要作用。PAK 4是一种致癌蛋白，与胃癌转移密切相关。然而，PAK 4调节胃癌转移的机制仍不完全清楚。本研究利用酵母双杂交系统鉴定了真核细胞延伸因子1 α 1（eEF 1A 1）是PAK 4的一个新的结合伴侣。通过GST pull-down和免疫共沉淀证实PAK 4和eEF 1A 1之间的相互作用。PAK 4与eEF 1A 1共定位于胃癌细胞的胞浆中。PAK 4的过表达增强了eEF 1A 1的表达水平，反之亦然。PAK 4和eEF 1A 1可能协同促进胃癌细胞的迁移和侵袭。采用免疫印迹法和免疫组化法检测PAK 4和eEF 1A 1在胃癌组织中的表达。统计学分析表明PAK 4和eEF 1A 1的表达呈正相关。本研究首次证明PAK 4与eEF 1A 1相互作用促进胃癌细胞的迁移和侵袭，从而为PAK 4和eEF 1A 1在胃癌进展中的功能提供了新的见解。
P21 activated kinase 4 (PAK4), as an effector of Cdc42, playing important roles in regulating the processes of cytoskeleton organization. PAK4 has been considered to be an oncogenic protein, which has strong relationship with gastric cancer metastasis. However, the mechanism of PAK4 in regulating gastric cancer metastasis is still not fully understood. In this study, using yeast two-hybrid system, we identified that the eukaryotic elongation factor 1 alpha 1 (eEF1A1) is a new binding partner of PAK4. The interaction between PAK4 and eEF1A1 was confirmed by GST pull-down and co-immunoprecipitation. PAK4 co-localized with eEF1A1 in the cytoplasm of gastric cancer cells. Overexpression of PAK4 enhanced the expression level of eEF1A1 and vice versa. PAK4 and eEF1A1 could cooperate to promote gastric cancer cell migration and invasion. Furthermore, the expression of PAK4 and eEF1A1 in clinical gastric cancer samples were examined by western blotting and immunohistochemistry. Statistical analysis indicated that there was positive correlation between the expression of PAK4 and eEF1A1. This study demonstrated for the first time that PAK4 interacted with eEF1A1 to promote migration and invasion of gastric cancer cells, thereby providing new insights into the function of PAK4 and eEF1A1 in the progression of gastric cancer.