Roles of the MEK1/2 and AKT pathways in CXCL12/CXCR4 induced cholangiocarcinoma cell invasion

doi:10.3748/wjg.v13.i10.1561

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Mar 14, 2007 (publication date) through May 6, 2024

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Gastroenterol. Mar 14, 2007; 13(10): 1561-1568
Published online Mar 14, 2007. doi: 10.3748/wjg.v13.i10.1561

Roles of the MEK1/2 and AKT pathways in CXCL12/CXCR4 induced cholangiocarcinoma cell invasion

Kawin Leelawat, Surang Leelawat, Siriluck Narong, Suradej Hongeng

Kawin Leelawat, Siriluck Narong, Department of Surgery, Rajavithi Hospital, Bangkok 10400, Thailand

Kawin Leelawat, Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok 10400, Thailand

Surang Leelawat, Faculty of Pharmacy, Rangsit University, Patumthani 12000, Thailand

Suradej Hongeng, Department of Pedriatric, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand

Author contributions: All authors contributed equally to the work.

Supported by the Grant from National Center for Genetic Engineering and Biotechnology, Thailand and Rajavithi Hospital Fund

Correspondence to: Kawin Leelawat, MD, PhD, Department of Surgery, Rajavithi Hospital, Bangkok 10400, Thailand. sckll@mahidol.ac.th

Telephone: +66-2-3548080 Fax: +66-2-3548080

Received: November 13, 2006
Revised: December 15, 2006
Accepted: February 12, 2007
Published online: March 14, 2007

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 PI3K 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.

Keywords: Cholangiocarcinoma, CXCR4, CXCL12, MEK1/2, PI3K