title: Activation of Rac1-PI3K/Akt is required for epidermal growth factor-induced PAK1 activation and cell migration in MDA-MB-231 breast cancer cells.
abstract: 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.
authors.affiliation: Department of Physiology.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yang
authors.forename: Jun
authors.initials: J
authors.lastname: Du
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Hu
authors.forename: Jiaojing
authors.initials: J
authors.lastname: Liu
authors.forename: Yinhui
authors.initials: Y
authors.lastname: Tian
authors.forename: Yichao
authors.initials: Y
authors.lastname: Zhu
authors.forename: Le
authors.initials: L
authors.lastname: Wang
authors.forename: Luo
authors.initials: L
authors.lastname: Gu
keywords: PI3K/Akt; Ras-related C3 botulinum toxin substrate 1 (Rac1); breast cancer cell; epidermal growth factor; migration; p21-actived kinase (PAK1)
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