Yang Yu, Du Jun, Hu Zhenzhen, Liu Jiaojing, Tian Yinhui, Zhu Yichao, Wang Le, Gu Luo
Department of Physiology.
J Biomed Res. 2011 Jul;25(4):237-45. doi: 10.1016/S1674-8301(11)60032-8.
Epidermal growth factor (EGF) may increase cell motility, an event implicated in cancer cell invasion and metastasis. However, the underlying mechanisms for EGF-induced cell motility remain elusive. In this study, we found that EGF treatment could activate Ras-related C3 botulinum toxin substrate 1 (Rac1), PI3K/Akt and p21-actived kinase (PAK1) along with cell migration. Ectopic expression of PAK1 K299R, a dominant negative PAK1 mutant, could largely abolish EGF-induced cell migration. Blocking PI3K/Akt signalling with LY294002 or Akt siRNA remarkably inhibited both EGF-induced PAK1 activation and cell migration. Furthermore, expression of dominant-negative Rac1 (T17N) could largely block EGF-induced PI3K/Akt-PAK1 activation and cell migration. Interestingly, EGF could induce a significant production of ROS, and N-acetyl-L-cysteine, a scavenger of ROS which abolished the EGF-induced ROS generation, cell migration, as well as activation of PI3K/Akt and PAK, but not Rac1. Our study demonstrated that EGF-induced cell migration involves a cascade of signalling events, including activation of Rac1, generation of ROS and subsequent activation of PI3K/Akt and PAK1.
表皮生长因子（EGF）可能会增加细胞运动性，这一事件与癌细胞的侵袭和转移有关。然而，EGF诱导细胞运动性的潜在机制仍不清楚。在本研究中，我们发现EGF处理可激活Ras相关的C3肉毒杆菌毒素底物1（Rac1）、PI3K/Akt和p21激活激酶（PAK1）以及细胞迁移。PAK1 K299R（一种显性负性PAK1突变体）的异位表达可在很大程度上消除EGF诱导的细胞迁移。用LY294002或Akt siRNA阻断PI3K/Akt信号通路可显著抑制EGF诱导的PAK1激活和细胞迁移。此外，显性负性Rac1（T17N）的表达可在很大程度上阻断EGF诱导的PI3K/Akt-PAK1激活和细胞迁移。有趣的是，EGF可诱导大量活性氧（ROS）的产生，而N-乙酰-L-半胱氨酸（一种ROS清除剂）可消除EGF诱导的ROS产生、细胞迁移以及PI3K/Akt和PAK的激活，但不能消除Rac1的激活。我们的研究表明，EGF诱导的细胞迁移涉及一系列信号事件，包括Rac1的激活、ROS的产生以及随后PI3K/Akt和PAK1的激活。
