Tumor Suppressive Function of p21-activated Kinase 6 in Hepatocellular Carcinoma.

Abstract	Our previous studies identified the oncogenic role of p21-activated kinase 1 (PAK1) in hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC). Contrarily, PAK6 was found to predict a favorable prognosis in RCC patients. Nevertheless, the ambiguous tumor suppressive function of PAK6 in hepatocarcinogenesis remains obscure. Herein, decreased PAK6 expression was found to be associated with tumor node metastasis stage progression and unfavorable overall survival in HCC patients. Additionally, overexpression and silence of PAK6 experiments showed that PAK6 inhibited xenografted tumor growth in vivo, and restricted cell proliferation, colony formation, migration, and invasion and promoted cell apoptosis and anoikis in vitro. Moreover, overexpression of kinase dead and nuclear localization signal deletion mutants of PAK6 experiments indicated the tumor suppressive function of PAK6 was partially dependent on its kinase activity and nuclear translocation. Furthermore, gain or loss of function in polycomb repressive complex 2 (PRC2) components, including EZH2, SUZ12, and EED, elucidated epigenetic control of H3K27me3-arbitrated PAK6 down-regulation in hepatoma cells. More importantly, negative correlation between PAK6 and EZH2 expression was observed in hepatoma tissues from HCC patients. These data identified the tumor suppressive role and potential underlying mechanism of PAK6 in hepatocarcinogenesis.
Authors	Weisi Liu, Yidong Liu, Haiou Liu, Weijuan Zhang, Qiang Fu, Jiejie Xu, Jianxin Gu
Journal	The Journal of biological chemistry (J Biol Chem) Vol. 290 Issue 47 Pg. 28489-28501 (Nov 20 2015) ISSN: 1083-351X [Electronic] United States
PMID	26442588 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright	© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
Chemical References	PAK6 protein, human p21-Activated Kinases
Topics	Animals Carcinoma, Hepatocellular (enzymology, pathology) Cell Division Cell Line, Tumor Female Genes, Tumor Suppressor Heterografts Humans Liver Neoplasms (enzymology, pathology) Male Mice Mice, Nude Middle Aged Survival Rate p21-Activated Kinases (metabolism)

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