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p21-activated protein kinases (PAKs) are activated by the small Rho family GTPases, Cdc42 and Rac1, in response to various extracellular signals and act in a variety of cellular processes including cell proliferation, morphology, motility, death and survival. PAK-4 is a newly identified Group II member of the PAK family. Like the Group I PAKs, PAK-4 contains an N-terminal p21 binding domain (PBD) and a C-terminal kinase domain, but lacks the auto-inhibitory domain (AID) which is present in Group I PAKs. Previous studies in fibroblasts have demonstrated that expression of activated form of PAK-4 promotes cell proliferation, anchorage-independent growth and cell migration, which are the characteristics of malignant tumors. Besides, PAK-4 was found to be frequently overexpressed in tumor cell lines. However, it is still not clear whether PAK-4 plays a role in the pathogenesis of human cancer. Here we report that PAK-4 is frequently over-expressed in hepatocellular carcinomas (HCCs), using real-time quantitative PCR and Western Blotting. To investigate the function of PAK-4 in the development of HCC, we established PAK-4 knocked-down stable cell lines, using vector-based siRNA approach. We report that knocking down of PAK-4 led to decrease in cell migration by trans-well assay. Morphological changes have also been observed after PAK-4 is knocked down. In summary these results incidated a possible tumorigenic effect of PAK-4 in HCC.Further studies are needed to address this issue and provide the molecular mechanism by which PAK-4 activity is regulated.

[Proc Amer Assoc Cancer Res, Volume 47, 2006]