|P21-activated protein kinase 1 is overexpressed in gastric cancer and induces cancer metastasis|
Authors: Liang-Hui Li, Qi Luo, Min-Hua Zheng, Chao Pan, Guo-Yang Wu, Yi-Zhuo Lu, Bo Feng, Xue-Hua Chen, Bing-Ya Liu
Affiliations: Department of General Surgery, Zhongshan Hospital, Xiamen University, Xiamen 361004, P.R. China, Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China, Department of Pathology, Zhongshan Hospital, Xiamen University, Xiamen 361004, P.R. China
Published online on: Friday, January 27, 2012
P21-activated protein kinase (Pak1), a main downstream effector of small Rho GTPases, plays an important role in the regulation of cell morphogenesis, motility, mitosis and angiogenesis. However, the role of Pak1 in gastric cancer metastasis remains unclear. Here, we showed that Pak1 is overexpressed in gastric cancer tissues from 74 patients by immunohistochemistry. Overexpression of Pak1 was associated with metastasis and prognosis of gastric cancer. In addition, overexpression of Pak1 increased gastric cancer cell motility and invasion, whereas downregulation of Pak1 expression reduced gastric cancer cell migration and invasion. In further study, data showed that activated Pak1 inhibited stress fiber and focal adhesion complex formation in gastric cancer cells and led to the formation of motile phenotypes. Importantly, activated Pak1 elicited phosphorylation of the ERK and JNK-dependent pathway in gastric cancer cell lines. In conclusion, our results suggest that Pak1 is overexpressed in gastric cancer and plays an important role in the metastasis of gastric cancer. The mechanism by which Pak1 induces cancer metastasis may involve activation of ERK and JNK.