Inactivation of lysyl oxidase by β-aminopropionitrile inhibits hypoxia-induced invasion and migration of cervical cancer cells

Yang,Xiaoxiao; Li,Shifeng; Li,Wande; Chen,Jingkao; Xiao,Xiao; Wang,Youqiong; Yan,Guangmei; Chen,Lijun

doi:10.3892/or.2012.2146

Inactivation of lysyl oxidase by β-aminopropionitrile inhibits hypoxia-induced invasion and migration of cervical cancer cells

Authors:
- Xiaoxiao Yang
- Shifeng Li
- Wande Li
- Jingkao Chen
- Xiao Xiao
- Youqiong Wang
- Guangmei Yan
- Lijun Chen
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Affiliations: Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510089, P.R. China, Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA
Published online on: November 19, 2012 https://doi.org/10.3892/or.2012.2146
Pages: 541-548

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Abstract

Tumor invasion and migration are major causes of mortality in patients with cervical carcinoma. Tumors under hypoxic conditions are more invasive and have a higher metastasic activity. Lysyl oxidase (LOX) is a hypoxia-responsive gene. LOX has been shown to be essential for hypoxia-induced metastasis in breast cancer. However, the direct impact of LOX on cervical cancer cell motility remains poorly understood. Our study revealed that LOX expression at protein and catalytic levels is upregulated in cervical cancer cells upon exposure to hypoxia. Hypoxia induced mesenchymal-like morphological changes in HeLa and SiHa cells which were accompanied by upregulation of α-SMA and vimentin, two mesenchymal markers, and downregulation of E-cadherin, an epithelial marker, indicating the epithelial-mesenchymal transition (EMT) of cervical cancer cells occurred under hypoxic conditions. Treatment of tumor cells with β-aminopropionitrile (BAPN), an active site inhibitor of LOX, blocked the hypoxia-induced EMT morphological and marker protein changes, and inhibited invasion and migration capacities of cervical carcinoma cells in vitro. Collectively, these findings suggest LOX enhances hypoxia-induced invasion and migration in cervical cancer cells mediated by the EMT which can be inhibited by BAPN.

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