NDLI: Rho-kinase 2 is frequently overexpressed in hepatocellular carcinoma and involved in tumor invasion.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Wong, Carmen Chak-Lui Wong, Chun-Ming Tung, Edmund Kwok-Kwan Man, Kwan Ng, Irene Oi-Lin
Description	Country affiliation: Hong Kong Author Affiliation: Wong CC ( Department of Pathology, Liver Cancer and Hepatitis Research Laboratory, The University of Hong Kong, Hong Kong.)
Abstract	UNLABELLED: Deregulation of Rho family small guanosine triphosphatases has been implicated in human carcinogenesis. Rho-kinases are downstream effectors of Rho guanosine triphosphatases in the regulation of cytoskeletal reorganization and cell motility. However, their functions in human cancers remain elusive. In this study, we aimed to investigate the role of Rho-kinases in hepatocellular carcinoma (HCC) tumor progression and invasion. We first examined the expression of the two Rho-kinases (ROCK1 and ROCK2) in human HCC, and found that ROCK2 was frequently overexpressed in primary HCCs (22/41 [53.66%]). Clinico-pathological analysis revealed that overexpression of ROCK2 was significantly associated with the presence of tumor microsatellite formation (P = 0.005), suggesting that deregulation of ROCK2 may contribute to the intrahepatic metastasis of HCC. Consistently, we demonstrated that stable overexpression of ROCK2 significantly enhanced cell motility and invasiveness in HCC cells. Conversely, stable knockdown of ROCK2 by short hairpin RNA approach remarkably reduced HCC cell migration and invasion. Moreover, orthotopic liver xenograft models provided further support that stable knockdown of ROCK2 suppressed HCC invasion in vivo. Stable knockdown of ROCK2 in HCC cells significantly inhibited Golgi reorientation, myosin phosphatase phosphorylation, and formations of stress fibers, filopodia, and lamellipodia; these molecular and cellular events are crucial for cell motility and cancer invasion. CONCLUSION: Our results indicate that ROCK2 was overexpressed in human HCCs, and this overexpression was associated with a more aggressive biological behavior. Our findings also demonstrate that ROCK2 played a significant role in regulating cytoskeletal events and contributed to the invasion of HCC.
File Format	HTM / HTML
ISSN	02709139
Issue Number	5
Volume Number	49
e-ISSN	15273350
Journal	Hepatology
Language	English
Publisher	Wiley
Publisher Date	2009-05-01
Publisher Place	United States
Access Restriction	Subscribed
Subject Keyword	Discipline Hepatology Carcinoma, Hepatocellular Enzymology Cell Movement Liver Neoplasms Neoplasm Invasiveness Rho-associated Kinases Metabolism Actins Animals Pathology Cell Line, Tumor Gene Knockdown Techniques Golgi Apparatus Physiology Humans Liver Mice Mice, Inbred Balb C Mice, Nude Myosin-light-chain Phosphatase Phosphorylation Pseudopodia Stress Fibers Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Hepatology

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