Abstract 3424: Slug-mediated epithelial mesenchymal transition in lung cancer cells

Abstract Epithelial-Mesenchymal Transition (EMT) has been classified as a unique process by which epithelial cells undergo mesenchymal phenotype leading to increased motility and invasion. The aim of this study was to elucidate the biological functions of Slug/Snail2 in lung cancer cells. We introduced Slug gene into several lung cancer cell line (A549, Ma1, and H1299) and established stable cell lines. Overexpression of Slug clearly mediated the EMT-related morphological changes including the cell scattering and the elongation of cell-shape. Real-time RT PCR and Western blot demonstrated that overexpression of Slug markedly downregulated the mRNA levels and protein levels of E-cadherin, while mesenchymal marker, N-cadherin, fibronectin 1 and vimentin, were upregulated. In addition to these changes, Slug enhanced the cellular migration activity and the cellular anchorage independent growth activity. Finally, we examined the Slug-mediated EMT on drug sensitivity to several anti-cancer dugs. Interestingly, Slug-overexpressing cells increased the drug sensitivity to only tubulin-binding agents such as vinorelbine, vincristine, and paclitaxel in vitro. Microarray analysis revealed that Slug downregulates tubulin beta 3 or 4 expression. Luciferase promoter assay showed that Slug directly down-regulates tubulin beta 4 expression at the transcription level. These results suggested that Slug-mediated sensitivity to tubulin-binding agents may be involved in expression changes of tubulin beta 3 or 4.In conclusion, we found that overexpression of Slug mediates EMT and change of drug sensitivity to tubulin-binding agents, presumably via downregulations of tubulin beta 3 and 4 in lung cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3424. doi:10.1158/1538-7445.AM2011-3424