Carcinogenesis Advance Access originally published online on December 16, 2004
Carcinogenesis 2005 26(3):681-687; doi:10.1093/carcin/bgi002
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Carcinogenesis vol.26 no.3 © Oxford University Press 2004; all rights reserved.
ARTICLE |
Significance of the Rac signaling pathway in HCC cell motility: implications for a new therapeutic target
1 Centre for the Study of Liver Disease, 2 Department of Surgery, 3 Department of Anatomy, 4 Department of Pathology and 5 Institute of Molecular Biology, University of Hong Kong, Pokfulam, Hong Kong, China
6 To whom correspondence should be addressed at: Department of Surgery, The University of Hong Kong, Queen Mary Hospital, L9-55, Faculty of Medicine Building, 21 Sassoon Road, Hong Kong, China. Tel: +86 852 2819 9646; Fax: +86 852 2819 9634; Email: kwanman{at}hkucc.hku.hk
Recurrence and metastasis are commonly associated with poor prognosis of hepatocellular carcinoma (HCC). Therefore, a better understanding of molecular mechanisms involved in HCC metastasis may lead to more effective treatment for HCC patients. Rac plays important roles in cytoskeletal reorganization leading to cell motility in renal and breast carcinomas. However, the role of Rac is controversial in tumors and has not been studied in HCC. The aim of this study was to investigate the importance of the Rac signaling pathway in HCC cell motility and the anti-metastatic potential of FTY720. Recently a pair of HCC cell lines from a primary tumor (H2P) and its matched metastasis (H2M) was established. These two cell lines provide a useful tool for the study of HCC metastasis. The results show that the Rac signaling pathway is activated in the metastatic HCC cell line (H2M) compared with the primary HCC cell line (H2P). FTY720 specifically suppressed H2M cell motility by down-regulation of the Rac–GTP level through inhibition of phosphoinositide 3-kinase activity. To conclude, this study is the first to demonstrate an essential role of Rac signaling pathway activation in HCC metastasis and suppression of cell motility by FTY720 through blocking of the Rac pathway.
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