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Article

Reactive oxygen species promote ovarian cancer progression via the HIF-1α/LOX/E-cadherin pathway

  • Authors:
    • Yu Wang
    • Jun Ma
    • Haoran Shen
    • Chengjie  Wang
    • Yueping  Sun
    • Stephen B. Howell
    • Xinjian Lin
  • View Affiliations / Copyright

    Affiliations: Department of Obstetrics and Gynecology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, P.R. China, Department of Cell Biology, Key Laboratory of the Education Ministry for Cell Differentiation and Apoptosis, Institutes of Medical Sciences, School of Medicine, Shanghai Jiaotong University, Shanghai, P.R. China, Department of Medicine and UC San Diego Moores Cancer Center, University of California-San Diego, La Jolla, CA, USA
  • Pages: 2150-2158
    |
    Published online on: August 28, 2014
       https://doi.org/10.3892/or.2014.3448
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Abstract

Reactive oxygen species (ROS) can drive the de‑differentiation of tumor cells leading to the process of epithelial-to-mesenchymal transition (EMT) to enhance invasion and metastasis. The invasive and metastatic phenotype of malignant cells is often linked to loss of E-cadherin expression, a hallmark of EMT. Recent studies have demonstrated that hypoxic exposure causes HIF-1-dependent repression of E-cadherin. However, the mechanism by which ROS and/or HIF suppresses E-cadherin expression remains less clear. In the present study, we found that ROS accumulation in ovarian carcinoma cells upregulated HIF-1α expression and subsequent transcriptional induction of lysyl oxidase (LOX) which repressed E-cadherin. Loss of E-cadherin facilitated ovarian cancer (OC) cell migration in vitro and promoted tumor growth in vivo. E-cadherin immunoreactivity correlated with International Federation of Gynecology and Obstetrics (FIGO) stage, tumor differentiation and metastasis. Negative E-cadherin expression along with FIGO stage, tumor differentiation and metastasis significantly predicted for a lower 5-year survival rate. These findings suggest that ROS play an important role in the initiation of metastatic growth of OC cells and support a molecular pathway from ROS to aggressive transformation which involves upregulation of HIF-1α and its downstream target LOX to suppress E-cadherin expression leading to an increase in cell motility and invasiveness.
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Copy and paste a formatted citation
Spandidos Publications style
Wang Y, Ma J, Shen H, Wang C, Sun Y, Howell SB and Lin X: Reactive oxygen species promote ovarian cancer progression via the HIF-1α/LOX/E-cadherin pathway. Oncol Rep 32: 2150-2158, 2014.
APA
Wang, Y., Ma, J., Shen, H., Wang, C., Sun, Y., Howell, S.B., & Lin, X. (2014). Reactive oxygen species promote ovarian cancer progression via the HIF-1α/LOX/E-cadherin pathway. Oncology Reports, 32, 2150-2158. https://doi.org/10.3892/or.2014.3448
MLA
Wang, Y., Ma, J., Shen, H., Wang, C., Sun, Y., Howell, S. B., Lin, X."Reactive oxygen species promote ovarian cancer progression via the HIF-1α/LOX/E-cadherin pathway". Oncology Reports 32.5 (2014): 2150-2158.
Chicago
Wang, Y., Ma, J., Shen, H., Wang, C., Sun, Y., Howell, S. B., Lin, X."Reactive oxygen species promote ovarian cancer progression via the HIF-1α/LOX/E-cadherin pathway". Oncology Reports 32, no. 5 (2014): 2150-2158. https://doi.org/10.3892/or.2014.3448
Copy and paste a formatted citation
x
Spandidos Publications style
Wang Y, Ma J, Shen H, Wang C, Sun Y, Howell SB and Lin X: Reactive oxygen species promote ovarian cancer progression via the HIF-1α/LOX/E-cadherin pathway. Oncol Rep 32: 2150-2158, 2014.
APA
Wang, Y., Ma, J., Shen, H., Wang, C., Sun, Y., Howell, S.B., & Lin, X. (2014). Reactive oxygen species promote ovarian cancer progression via the HIF-1α/LOX/E-cadherin pathway. Oncology Reports, 32, 2150-2158. https://doi.org/10.3892/or.2014.3448
MLA
Wang, Y., Ma, J., Shen, H., Wang, C., Sun, Y., Howell, S. B., Lin, X."Reactive oxygen species promote ovarian cancer progression via the HIF-1α/LOX/E-cadherin pathway". Oncology Reports 32.5 (2014): 2150-2158.
Chicago
Wang, Y., Ma, J., Shen, H., Wang, C., Sun, Y., Howell, S. B., Lin, X."Reactive oxygen species promote ovarian cancer progression via the HIF-1α/LOX/E-cadherin pathway". Oncology Reports 32, no. 5 (2014): 2150-2158. https://doi.org/10.3892/or.2014.3448
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