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.