Journal Article

Significance of the Rac signaling pathway in HCC cell motility: implications for a new therapeutic target

Terence K. Lee, Kwan Man, Joanna W. Ho, Xiang Hong Wang, Ronnie T. Poon, Chris K. Sun, Kevin T. Ng, Irene O. Ng, Ray Xu and Sheung Tat Fan

in Carcinogenesis

Volume 26, issue 3, pages 681-687
Published in print March 2005 | ISSN: 0143-3334
Published online March 2005 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgi002
Significance of the Rac signaling pathway in HCC cell motility: implications for a new therapeutic target

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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.

Keywords: ECM, extracellular matrix; HCC, hepatocellular carcinoma; PAK, p21 activated kinase 1; PBS, phosphate-buffered saline; PI3-K, phosphoinositide 3-kinase; Rac-DA, dominant active Rac; Rac-DN, dominant negative Rac; S1P, sphingosine 1-phosphate

Journal Article.  4207 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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