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

  • Published online on: August 28, 2014     https://doi.org/10.3892/or.2014.3448
  • Pages: 2150-2158
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


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.
View Figures
View References

Related Articles

Journal Cover

November-2014
Volume 32 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

Sign up for eToc alerts

Recommend to Library

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