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Contact: Jin-Lei Wang
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World Journal of Gastroenterology

Different signaling pathways of cholangiocarcinoma

Cholangiocarcinoma (CCA), a bile duct cancer, is one of the major cancers in Northeast Thailand. This cancer is difficult to diagnose and has high metastatic and mortality rates. Overexpression of Met, a hepatocyte growth factor (HGF) receptor, has frequently been found in CCA and is correlated with progression of this type of cancer. HGF/Met activation induces a variety of cellular processes, including cell scattering, invasion and proliferation. Although a number of studies have been reported regarding the correlation between Met expression and CCA, the molecular mechanisms by which HGF induces CCA invasion are not completely understood.

A research article published on February 14, 2010 in the World Journal of Gastroenterology addresses this question. The research team led by Dr. Suthiphongchai T from Mahidol University used two CCA cell lines overexpressing Met, KKU-M213 and HuCCA-1, to study the role of Met in CCA invasion by activating the Met pathway with HGF. HGF strongly induced invasion and motility of the two CCA cell lines and concomitantly altered E-cadherin localization from membrane to cytosol, but did not affect the levels of secreted MMP-2, MMP-9 or uPA.

Signaling pathways responsible for HGF-induced invasion were further investigated. HGF induced ERK and PI3K/Akt pathways of both CCA cell lines but with different kinetic profiles. HGF induced sustained ERK activation in the KKU-M213 cell line, but transient ERK activation in HuCCA-1 cells. Using specific inhibitors of PI3K and ERK pathways, it was shown that HGF-induced invasion of KKU-M213 was strongly inhibited by both inhibitors, while that of HuCCA-1 was strongly inhibited by PI3K inhibitor but only weakly inhibited by ERK inhibitor. Thus, the signaling pathways responsible for HGF-induced invasiveness of the two CCA cell lines were different, in that PI3K pathway was common for both cell lines, whereas the role of ERK1/2 was likely to be dependent on the duration of ERK1/2 activation.

These results provided more information on the understanding of the signaling mechanisms responsible for HGF-induced CCA invasiveness, which may be helpful for identifying better targets for CCA therapy and for designing appropriate therapeutic strategy to suit each individual patient.

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Reference: Menakongka A, Suthiphongchai T. Involvement of PI3K and ERK1/2 pathways in hepatocyte growth factor-induced cholangiocarcinoma cell invasion. World J Gastroenterol 2010; 16(6): 713-722

http://www.wjgnet.com/1007-9327/16/713.asp

Correspondence to: Tuangporn Suthiphongchai, Associate Professor, Department of Biochemistry, Faculty of Science, Mahidol University, 272 Rama 6 Road, Bangkok 10400, Thailand. sctsc@mahidol.ac.th

Telephone: +662-2015609 Fax: +662-3547174

About World Journal of Gastroenterology

World Journal of Gastroenterology (WJG), a leading international journal in gastroenterology and hepatology, has established a reputation for publishing first class research on esophageal cancer, gastric cancer, liver cancer, viral hepatitis, colorectal cancer, and H. pylori infection and provides a forum for both clinicians and scientists. WJG has been indexed and abstracted in Current Contents/Clinical Medicine, Science Citation Index Expanded (also known as SciSearch) and Journal Citation Reports/Science Edition, Index Medicus, MEDLINE and PubMed, Chemical Abstracts, EMBASE/Excerpta Medica, Abstracts Journals, Nature Clinical Practice Gastroenterology and Hepatology, CAB Abstracts and Global Health. ISI JCR 2008 IF: 2.081. WJG is a weekly journal published by WJG Press. The publication dates are the 7th, 14th, 21st, and 28th day of every month. WJG is supported by The National Natural Science Foundation of China, No. 30224801 and No. 30424812, and was founded with the name of China National Journal of New Gastroenterology on October 1, 1995, and renamed WJG on January 25, 1998.

About The WJG Press

The WJG Press mainly publishes World Journal of Gastroenterology.



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