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Different signaling pathways of cholangiocarcinoma

March 4, 2010
World Journal of Gastroenterology
Overexpression of receptor tyrosine kinase Met has frequently been found in cholangiocarcinoma. A research group in Thailand demonstrated that hepatocyte growth factor, a Met ligand, induced invasion and motility and altered E-cadherin localization in two cholangiocarcinoma cell lines, without having any significant effects on levels of two secreted matrix metalloproteinases. However, the signaling pathways underlying HGF-induced invasiveness of the two cell lines were different.

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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The above post is reprinted from materials provided by World Journal of Gastroenterology. Note: Materials may be edited for content and length.

Journal Reference:

  1. Menakongka A, Suthiphongchai T. Involvement of PI3K and ERK1/2 pathways in hepatocyte growth factor-induced cholangiocarcinoma cell invasion. World Journal of Gastroenterology, 2010; 16 (6): 713 DOI: 10.3748/wjg.v16.i6.713

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World Journal of Gastroenterology. "Different signaling pathways of cholangiocarcinoma." ScienceDaily. ScienceDaily, 4 March 2010. <>.
World Journal of Gastroenterology. (2010, March 4). Different signaling pathways of cholangiocarcinoma. ScienceDaily. Retrieved November 30, 2015 from
World Journal of Gastroenterology. "Different signaling pathways of cholangiocarcinoma." ScienceDaily. (accessed November 30, 2015).

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