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Article

Upregulation of Wnt signaling under hypoxia promotes lung cancer progression

  • Authors:
    • Chun-Fu Hong
    • Wei-You Chen
    • Cheng-Wen Wu
  • View Affiliations / Copyright

    Affiliations: Department of Long-Term Care, National Quemoy University, Kinmen County 89250, Taiwan, R.O.C., Institute of Biochemistry and Molecular Biology, National Yang Ming University, Taipei 11221, Taiwan, R.O.C.
  • Pages: 1706-1714
    |
    Published online on: July 12, 2017
       https://doi.org/10.3892/or.2017.5807
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Abstract

The hypoxic tumor microenvironment induces epithelial-mesenchymal transition (EMT) in tumor cells and increases tumor cell malignancy. Previous studies indicated that malfunction of Wnt signaling is observed in some lung cancer patients. Athough crosstalk between hypoxia and Wnt signaling in tumor cells has recently been revealed, the detailed underlying mechanisms have not been well defined. In the present study, we demonstrated that hypoxia in lung adenocarcinoma cells can enhance Wnt signaling activity by stabilizing β-catenin and altering its localization into the nucleus. Overexpression of HIF-2α increased β-catenin expression, promoted cell mobility, and induced morphological changes to a greater degree than HIF-1α overexpression. Knockdown of HIF-2α decreased β-catenin expression and inhibited hypoxia-induced cell mobility. Moreover, we identified that phosphorylational activation of AKT1 by hypoxia and HIF-2α was required for Wnt activation upon hypoxia treatment. Downregulation of HIF-2α and β-catenin reduced colony formation when cells were exposed to long-term hypoxia treatment. Taken together, our data support that hypoxia activates PI3K/AKT as well as Wnt signaling in a HIF-2α-dependent manner, thus elevating the resistance of lung cancer cells to chronic hypoxia-induced stress.
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Copy and paste a formatted citation
Spandidos Publications style
Hong C, Chen W and Wu C: Upregulation of Wnt signaling under hypoxia promotes lung cancer progression. Oncol Rep 38: 1706-1714, 2017.
APA
Hong, C., Chen, W., & Wu, C. (2017). Upregulation of Wnt signaling under hypoxia promotes lung cancer progression. Oncology Reports, 38, 1706-1714. https://doi.org/10.3892/or.2017.5807
MLA
Hong, C., Chen, W., Wu, C."Upregulation of Wnt signaling under hypoxia promotes lung cancer progression". Oncology Reports 38.3 (2017): 1706-1714.
Chicago
Hong, C., Chen, W., Wu, C."Upregulation of Wnt signaling under hypoxia promotes lung cancer progression". Oncology Reports 38, no. 3 (2017): 1706-1714. https://doi.org/10.3892/or.2017.5807
Copy and paste a formatted citation
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Spandidos Publications style
Hong C, Chen W and Wu C: Upregulation of Wnt signaling under hypoxia promotes lung cancer progression. Oncol Rep 38: 1706-1714, 2017.
APA
Hong, C., Chen, W., & Wu, C. (2017). Upregulation of Wnt signaling under hypoxia promotes lung cancer progression. Oncology Reports, 38, 1706-1714. https://doi.org/10.3892/or.2017.5807
MLA
Hong, C., Chen, W., Wu, C."Upregulation of Wnt signaling under hypoxia promotes lung cancer progression". Oncology Reports 38.3 (2017): 1706-1714.
Chicago
Hong, C., Chen, W., Wu, C."Upregulation of Wnt signaling under hypoxia promotes lung cancer progression". Oncology Reports 38, no. 3 (2017): 1706-1714. https://doi.org/10.3892/or.2017.5807
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