P21-activated protein kinase 1 induces colorectal cancer metastasis involving ERK activation and phosphorylation of FAK at Ser-910.
Pak1 has been reported to be overexpressed in colorectal cancer, but the role of Pak1 in colorectal cancer remains unclear. In this study, Pak1 expression and activity were associated with aggressive behavior of colorectal cancer. Overexpression of Pak1 increased colorectal cancer cell motility and invasion, whereas down-regulation of Pak1 expression or activity reduced colorectal cancer cell migration and invasion. In addition, activated Pak1 inhibited stress fiber and focal adhesion complex formation in colorectal cancer cells and led to formation of motile phenotypes. Importantly, activated Pak1 elicited phosphorylation of FAK at Ser-910 via an ERK-dependent pathway in colorectal cancer cell lines and clinical samples. In conclusion, our results suggest that activated Pak1 regulates colorectal cancer metastasis requiring an ERK-dependent phosphorylation of FAK at Ser-910.
Li
Liang-Hui
LH
Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, PR China.
Zheng
Min-Hua
MH
Luo
Qi
Q
Ye
Qing
Q
Feng
Bo
B
Lu
Ai-Guo
AG
Wang
Ming-Liang
ML
Chen
Xue-Hua
XH
Su
Li-Ping
LP
Liu
Bing-Ya
BY
D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000556:secondary; D004789:Enzyme Activation; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D022001:Focal Adhesions / Q000201:enzymology; D006801:Humans; D008297:Male; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010641:Phenotype; D010766:Phosphorylation; D034622:RNA Interference; D012694:Serine; D022502:Stress Fibers / Q000201:enzymology; D014162:Transfection; D054462:p21-Activated Kinases / Q000235:genetics / Q000378:metabolism*
D012694:Serine; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; C515903:PAK1 protein, human; D054462:p21-Activated Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3