Activation of Rac1-PI3K/Akt is required for epidermal growth factorinduced PAK1 activation and cell migration in MDA-MB-231 breast cancer cells

作     者：Yu Yang Jun Du Zhenzhen Hu Jiaojing Liu Yinhui Tian Yichao Zhu Le Wang Luo Gu 

作者机构：Department of Physiology Nanjing Medical University Nanjing Jiangsu 210029 China Cancer Center Nanjing Medical University Nanjing Jiangsu 210029 China 

出 版 物：《The Journal of Biomedical Research》 (生物医学研究杂志（英文版）)

年 卷 期：2011年第25卷第4期

页      面：237-245页

学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 071009[理学-细胞生物学] 09[农学] 0901[农学-作物学] 090102[农学-作物遗传育种] 

基　　金：supported by grants from the National Natural Science Foundation of China (No. 30872926) the Program for AdvancedTalents within Six Industries of Jiangsu Province (08-D) to Dr. Luo Gu the Science Development Foundation of Nanjing Medical University (No. 2010NJMUZ35) the Research Program funded by Schoolof Basic Medical Science, Nanjing Medical University to Dr. Jun Du 

主　　题：breast cancer cell epidermal growth factor migration Ras-related C3 botulinum toxin substrate 1(Rac1) PI3K/Akt p21-actived kinase (PAK1) 

摘      要：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 （Racl）, 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 Racl （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 Racl. Our study demonstrated that EGF-induced cell migration involves a cascade of signalling events, including activation of Racl, generation of ROS and subsequent activation of PI3K/Akt and PAK1.