Publication: Hypoxia enhances cholangiocarcinoma invasion through activation of hepatocyte growth factor receptor and the extracellular signal-regulated kinase signaling pathway
Issued Date
2015-09-01
Resource Type
ISSN
17913004
17912997
17912997
Other identifier(s)
2-s2.0-84935447626
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Molecular Medicine Reports. Vol.12, No.3 (2015), 3265-3272
Suggested Citation
Thitinee Vanichapol, Kawin Leelawat, Suradej Hongeng Hypoxia enhances cholangiocarcinoma invasion through activation of hepatocyte growth factor receptor and the extracellular signal-regulated kinase signaling pathway. Molecular Medicine Reports. Vol.12, No.3 (2015), 3265-3272. doi:10.3892/mmr.2015.3865 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/35390
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Hypoxia enhances cholangiocarcinoma invasion through activation of hepatocyte growth factor receptor and the extracellular signal-regulated kinase signaling pathway
Author(s)
Other Contributor(s)
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.