Activation of Rac1-P13K/Akt is required for epidermal growth factor induced PAK1 activation and cell migration in MDA-MB-231 breast cancer cells
Yu Yang
Jun Du
Zhenzhen Hu
Jiaojing Liu
Yinhui Tian
Yiehao Zhu
Le Wang
Luo Gu
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 I (Racl), PI3K/Akt and p21-actived kinase (PAKl) along with cell migration. Ectopic expression of PAKI K299R, a dominant negative PAKl mutant, could largely abolish EGF-induced cell migration. Blocking PI3K/Akt signalling with LY294002 or Akt siRNA remarkably inhibited both EGF-induced PAKl activation and cell migration. Furthermore, expression of dominant-negative Racl (T17N) could largely block EGF-induced PI3K/Akt-PAKl 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 PAKl.
机标关键词：breast cancer cellsMDA-MB-231cell migrationPAK1epidermal growth factorPI3K/AktEGFcell motility
分类号：R737.9(泌尿生殖器肿瘤)
资助基金：grants from the National Natural Science Foundation of China(30872926)the Program for Advanced Talents within Six Industries of Jiangsu Province (0S-D)
论文发表日期：2011-01-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
英文信息