期刊
JOURNAL OF BIOMEDICAL RESEARCH
卷 25, 期 4, 页码 237-245出版社
NANJING MEDICAL UNIV
DOI: 10.1016/S1674-8301(11)60032-8
关键词
breast cancer cell; epidermal growth factor; migration; Ras-related C3 botulinum toxin substrate 1 (Rac1); PI3K/Akt; p21-actived kinase (PAK1)
资金
- National Natural Science Foundation of China [30872926]
- Program for Advanced Talents within Six Industries of Jiangsu Province [08-D]
- Science Development Foundation of Nanjing Medical University [2010NJMUZ35]
- School of Basic Medical Science, Nanjing Medical University
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.
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