Abstract
BackgroundEpithelial to mesenchymal transition (EMT) has been shown to be a crucial enhancing mechanism in the process of cancer metastasis, as it increases cancer cell capabilities to migrate, invade and survive in circulating systems. This study aimed to investigate the effect of essential element zinc on EMT characteristics in lung cancer cells.MethodsThe effect of zinc on EMT was evaluated by determining the EMT behaviors using migration, invasion and colony formation assay. EMT markers were examined by western blot analysis. Reactive oxygen species (ROS) were detected by specific fluorescence dyes and flow cytometry. All results were analyzed by ANOVA, followed by individual comparisons with post hoc test.ResultsThe present study has revealed for the first time that the zinc could induce EMT and related metastatic behaviors in lung cancer cells. Results showed that treatment of the cells with zinc resulted in the significant increase of EMT markers N-cadherin, vimentin, snail and slug and decrease of E-cadherin proteins. Zinc-treated cells exhibited the mesenchymal-like morphology and increased cancer cell motility with significant increase of activated FAK, Rac1, and RhoA. Also, tumorigenic abilities of lung cancer cells could be enhanced by zinc. Importantly, the underlying mechanism was found to be caused by the ability of zinc to generate intracellular superoxide anion. Zinc was shown to induce cellular superoxide anion generation and the up-regulation of EMT markers and the induced cell migration and invasion in zinc-treated cells could be attenuated by the treatment of MnTBAP, a specific superoxide anion inhibitor.ConclusionKnowledge gains from this study may highlight the roles of this important element in the regulation of EMT and cancer metastasis and fulfill the understanding in the area of cancer cell biology.
Highlights
Epithelial to mesenchymal transition (EMT) has been shown to be a crucial enhancing mechanism in the process of cancer metastasis, as it increases cancer cell capabilities to migrate, invade and survive in circulating systems
Evidence indicates that several zinc influx transporters such as Zrt/Irt-like protein (ZIP) 6 [12], ZIP7 [13] and ZIP10 [14] were shown to be upregulated in cancer cells and their high levels correlate with aggressive behaviors and poor prognosis
Effects of zinc on viability of human lung cancer H460 cells In order to investigate the effect of zinc on EMT phenotypes in human lung cancer cells, we first evaluated the non-cytotoxic concentrations of zinc
Summary
Epithelial to mesenchymal transition (EMT) has been shown to be a crucial enhancing mechanism in the process of cancer metastasis, as it increases cancer cell capabilities to migrate, invade and survive in circulating systems. This study aimed to investigate the effect of essential element zinc on EMT characteristics in lung cancer cells. Evidence indicates that several zinc influx transporters such as Zrt/Irt-like protein (ZIP) 6 [12], ZIP7 [13] and ZIP10 [14] were shown to be upregulated in cancer cells and their high levels correlate with aggressive behaviors and poor prognosis. Such data has suggested the roles of zinc in regulation of cancer cell biology. Effects of zinc on the EMT process of cancer cells are largely unknown
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