Open Access

Hypoxia enhances cholangiocarcinoma invasion through activation of hepatocyte growth factor receptor and the extracellular signal‑regulated kinase signaling pathway

  • Authors:
    • Thitinee Vanichapol
    • Kawin Leelawat
    • Suradej Hongeng
  • View Affiliations

  • Published online on: May 27, 2015     https://doi.org/10.3892/mmr.2015.3865
  • Pages: 3265-3272
  • Copyright: © Vanichapol et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Hypoxia is associated with tumor progression and poor prognosis in several cancer types. The present study aimed to examine the contribution of hypoxia (1% O2) to cancer progression in a cholangiocarcinoma cell line, RMCCA‑1. The molecular basis of the hypoxic response pathway was investigated. The results showed that hypoxia significantly accelerated cancer cell proliferation and enhanced cell invasion (P<0.05). By using receptor tyrosine kinase and intracellular signaling antibody array kits, an increased phosphorylation/activation of a number of signaling molecules, particularly hepatocyte growth factor receptor (Met) and extracellular signal‑regulated kinase (ERK) 1/2, was identified. Inhibition of Met and ERK by small hairpin RNA and U0126, respectively, significantly inhibited hypoxia‑induced the invasive potential of RMCCA‑1 cells (P<0.05). However, according to immunohistochemical analysis, hypoxia‑inducible factor‑1α expression was not correlated with cancer staging or tumor differentiation in 44 samples of cholangicarcinoma cases. The findings of the present study emphasized the importance of Met/ERK pathway activation as a key molecular event that may be responsible for a more invasive phenotype in hypoxic tumors and suggest Met as a potential target for the treatment of cholangiocarcinoma.
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September-2015
Volume 12 Issue 3

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Vanichapol T, Leelawat K and Hongeng S: Hypoxia enhances cholangiocarcinoma invasion through activation of hepatocyte growth factor receptor and the extracellular signal‑regulated kinase signaling pathway. Mol Med Rep 12: 3265-3272, 2015
APA
Vanichapol, T., Leelawat, K., & Hongeng, S. (2015). Hypoxia enhances cholangiocarcinoma invasion through activation of hepatocyte growth factor receptor and the extracellular signal‑regulated kinase signaling pathway. Molecular Medicine Reports, 12, 3265-3272. https://doi.org/10.3892/mmr.2015.3865
MLA
Vanichapol, T., Leelawat, K., Hongeng, S."Hypoxia enhances cholangiocarcinoma invasion through activation of hepatocyte growth factor receptor and the extracellular signal‑regulated kinase signaling pathway". Molecular Medicine Reports 12.3 (2015): 3265-3272.
Chicago
Vanichapol, T., Leelawat, K., Hongeng, S."Hypoxia enhances cholangiocarcinoma invasion through activation of hepatocyte growth factor receptor and the extracellular signal‑regulated kinase signaling pathway". Molecular Medicine Reports 12, no. 3 (2015): 3265-3272. https://doi.org/10.3892/mmr.2015.3865