ArticleMolecular medicine reports2015
Hypoxia enhances cholangiocarcinoma invasion through activation of hepatocyte growth factor receptor and the extracellular signal‑regulated kinase signaling pathway.
Article in Molecular medicine reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- Harnessing cellular immunotherapy for cholangiocarcinoma: an integrated roadmap for overcoming resistance.Frontiers in immunology · 2026Review
- Frequent EPHA2 receptor mutations in cholangiocarcinoma disrupt receptor forward signaling supporting a tumor suppressor role.Biochimica et biophysica acta. Molecular cell research · 2026Article
- Unlocking the Therapeutic Potential of DNA-PKcs in Cancer: Comprehensive Insights into Mechanisms and Clinical Applications.Cancers · 2025Review
- ERK1/2 Signaling in Intrahepatic Cholangiocarcinoma: From Preclinical Advances to Therapeutic Strategies.Biology · 2025Review
- Organoids and spheroids: advancedFrontiers in cell and developmental biology · 2024Review
- Single-cell RNA sequencing identifies critical transcription factors of tumor cell invasion induced by hypoxia microenvironment in glioblastoma.Theranostics · 2023Article
- Locoregional Therapy in the Management of Intrahepatic Cholangiocarcinoma: Is There Sufficient Evidence to Guide Current Clinical Practice?Current oncology reports · 2022Review
- YAP1 activation and Hippo pathway signaling in the pathogenesis and treatment of intrahepatic cholangiocarcinoma.Advances in cancer research · 2022Review
- The Role of the Hedgehog Pathway in Cholangiocarcinoma.Cancers · 2021Review
- Targeting Hypoxia Using Evofosfamide and Companion Hypoxia Imaging of FMISO-PET in Advanced Biliary Tract Cancer.Cancer research and treatment · 2021Article
- Review
- Liver Tumor Microenvironment.Advances in experimental medicine and biology · 2020Article
- Role of Glucose Metabolism Reprogramming in the Pathogenesis of Cholangiocarcinoma.Frontiers in medicine · 2020Review
- MEK inhibition suppresses K-Ras wild-type cholangiocarcinoma in vitro and in vivo via inhibiting cell proliferation and modulating tumor microenvironment.Cell death & disease · 2019Article
- The role of tumour microenvironment: a new vision for cholangiocarcinoma.Journal of cellular and molecular medicine · 2019Review
- Potential role of HIF-1-responsive microRNA210/HIF3 axis on gemcitabine resistance in cholangiocarcinoma cells.PloS one · 2018Article
- Immune Escape Mechanisms and Future Prospects for Immunotherapy in Neuroblastoma.BioMed research international · 2018Review
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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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