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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/24944
Title: Roles of the MEK1/2 and AKT pathways in CXCL12/CXCR4 induced cholangiocarcinoma cell invasion
Authors: Kawin Leelawat
Surang Leelawat
Siriluck Narong
Suradej Hongeng
Rajavithi Hospital
Mahidol University
Rangsit University
Keywords: Medicine
Issue Date: 14-Mar-2007
Citation: World Journal of Gastroenterology. Vol.13, No.10 (2007), 1561-1568
Abstract: Aim: To evaluate the expression of C-X-C motif chemokine receptor 4 (CXCR4) and its signaling cascades, which were previously identified as a key factor for cancer cell progression and metastasis, in cholangiocarcinoma cell lines. Methods: The expression of CXCR4 and its signaling cascades were determined in the cholangiocarcinoma cell lines (RMCCA1 and KKU100) by Western blotting. The invasion assays and the detection of actin polymerization were tested in these cholangiocarcinoma cells treated with CXC chemokine ligand -12 (CXCL12). Results: Expression of CXCR4 was detected in both cholangiocarcinoma cell lines and activation of CXCR4 with CXCL12 triggered the signaling via the extracellular signal-regulated kinase-1/2 (ERK1/2) and phosphoinositide 3-kinase (PI3K) and induction of cholangiocarcinoma cell invasion, and displayed high levels of actin polymerization. Addition of CXCR4 inhibitor (AMD3100) abrogated CXCL12-induced phosphorylation of MEK1/2 and Akt in these cells. Moreover, treatment with MEK1/2 inhibitor (U0126) or P13K inhibitor (LY294002) also attenuated the effect of CXCL12-induced cholangiocarcinoma cell invasion. Conclusion: These results indicated that the activation of CXCR4 and its signaling pathways (MEK1/2 and Akt) are essential for CXCL12-induced cholangiocarcinoma cell invasion. This rises Implications on a potential role for the inhibition of CXCR4 or its signal cascades in the treatment of cholangiocarcinoma. © 2007 The WJG Press. All rights reserved.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=34247600489&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/24944
ISSN: 10079327
Appears in Collections:Scopus 2006-2010

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