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International Journal of Oncology
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Article

Hypoxia inducible factor 1α-mediated LOX expression correlates with migration and invasion in epithelial ovarian cancer

  • Authors:
    • Fang Ji
    • You Wang
    • Lihua Qiu
    • Shu Li
    • Jing Zhu
    • Zhou Liang
    • Yinsheng Wan
    • Wen Di
  • View Affiliations / Copyright

    Affiliations: Department of Obstetrics and Gynecology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China, Department of Biology, Providence College, Providence, RI 02918, USA
  • Pages: 1578-1588
    |
    Published online on: March 29, 2013
       https://doi.org/10.3892/ijo.2013.1878
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Abstract

This study investigated the role of LOX in promoting invasion and metastasis of epithelial ovarian cancer in a hypoxic environment and its specific signal transduction pathway. Immunohistochemical detection of HIF-1α and LOX protein expression was performed on formalin-fixed paraffin sections of normal ovary, benign ovarian tumors, borderline and malignant epithelial ovarian tumor paraffin sample, using Mann-Whitney U test for independent comparisons and Wilcoxon signed-ranks test for paired comparisons. HIF-1α and LOX were knocked down in epithelial ovarian cancer cells (EOC), and HIF-1α/LOX regulation mechanism and LOX catalytic activity under hypoxia/reoxygenation microenvironment were explored. Cell migration and invasion ability in LOX inhibited HO8910 cells were investigated under hypoxia/reoxygenation conditions, using matrigel cell invasion and migration assays. We found that HIF-1α and LOX are highly expressed in epithelial ovarian cancer tissues, and the expression of both proteins is significantly correlated with the tumor grade, tumor diameter and lymph node metastasis. HIF-1α expression is positively correlated with the expression of LOX. Specifically, the expression of LOX and HIF-1α markedly increases under hypoxic conditions and decreases after reoxygenation. siRNA knockdown of LOX or β-aminoproprionitrile (βAPN), an inhibitor of LOX activity, that attenuates LOX activity, downregulates HIF-1α protein expression and inhibits HO8910 migratory and invasive abilities. LOX catalytic activity is significantly reduced under hypoxic conditions. Moreover, EOC cells display a marked increase in LOX-dependent FAK/AKT activation and cell migration following hypoxia/reoxygenation. Collectively, our study demonstrates that the hypoxia-HIF-1α, LOX-FAK/AKT pathway regulates the migration and invasion of epithelial ovarian cancer cells under hypoxia/reoxygenation conditions, thus, promoting metastasis of ovarian cancer.
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Copy and paste a formatted citation
Spandidos Publications style
Ji F, Wang Y, Qiu L, Li S, Zhu J, Liang Z, Wan Y and Di W: Hypoxia inducible factor 1α-mediated LOX expression correlates with migration and invasion in epithelial ovarian cancer. Int J Oncol 42: 1578-1588, 2013.
APA
Ji, F., Wang, Y., Qiu, L., Li, S., Zhu, J., Liang, Z. ... Di, W. (2013). Hypoxia inducible factor 1α-mediated LOX expression correlates with migration and invasion in epithelial ovarian cancer. International Journal of Oncology, 42, 1578-1588. https://doi.org/10.3892/ijo.2013.1878
MLA
Ji, F., Wang, Y., Qiu, L., Li, S., Zhu, J., Liang, Z., Wan, Y., Di, W."Hypoxia inducible factor 1α-mediated LOX expression correlates with migration and invasion in epithelial ovarian cancer". International Journal of Oncology 42.5 (2013): 1578-1588.
Chicago
Ji, F., Wang, Y., Qiu, L., Li, S., Zhu, J., Liang, Z., Wan, Y., Di, W."Hypoxia inducible factor 1α-mediated LOX expression correlates with migration and invasion in epithelial ovarian cancer". International Journal of Oncology 42, no. 5 (2013): 1578-1588. https://doi.org/10.3892/ijo.2013.1878
Copy and paste a formatted citation
x
Spandidos Publications style
Ji F, Wang Y, Qiu L, Li S, Zhu J, Liang Z, Wan Y and Di W: Hypoxia inducible factor 1α-mediated LOX expression correlates with migration and invasion in epithelial ovarian cancer. Int J Oncol 42: 1578-1588, 2013.
APA
Ji, F., Wang, Y., Qiu, L., Li, S., Zhu, J., Liang, Z. ... Di, W. (2013). Hypoxia inducible factor 1α-mediated LOX expression correlates with migration and invasion in epithelial ovarian cancer. International Journal of Oncology, 42, 1578-1588. https://doi.org/10.3892/ijo.2013.1878
MLA
Ji, F., Wang, Y., Qiu, L., Li, S., Zhu, J., Liang, Z., Wan, Y., Di, W."Hypoxia inducible factor 1α-mediated LOX expression correlates with migration and invasion in epithelial ovarian cancer". International Journal of Oncology 42.5 (2013): 1578-1588.
Chicago
Ji, F., Wang, Y., Qiu, L., Li, S., Zhu, J., Liang, Z., Wan, Y., Di, W."Hypoxia inducible factor 1α-mediated LOX expression correlates with migration and invasion in epithelial ovarian cancer". International Journal of Oncology 42, no. 5 (2013): 1578-1588. https://doi.org/10.3892/ijo.2013.1878
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