Abstract 2300: Overexpression of Snail induces epithelial-mesenchymal transition and cancer stem cell-like phenotypes in CRC cells

Abstract

Abstract Background: Epithelial-to-mesenchymal transition (EMT) is a critical process providing tumor cells with the ability to migrate and escape from the primary tumor and metastasize to distant sites. Recently, EMT has been shown to be associated with the cancer stem cell (CSC) phenotype in breast cancer. Snail is a transcriptional factor that mediates EMT in a number of tumor types. Its aberrant expression has been found in various cancers including colorectal cancer (CRC). The role of Snail in mediating EMT and CSC function in CRC has not yet been fully elucidated. Methods: The human CRC cell lines HT29 and KM12L4 were transduced with a retrovirus containing the pBabe-puro-Snail expression construct or the empty vector. The Snail expressing cells and controls were selected with the medium containing 2µg/ml puromycin. Changes in cell proliferation and chemo-sensitivity were determined by MTT assay. Migration and invasion were determined using in vitro wound healing assay and modified Boyden Chamber assays, respectively. EMT makers (E-cadherin, vimentin) and the putative CSC marker CD133 was analyzed by Western blotting. ALDH1 enzyme activity was analyzed by the Aldefluor assay. Results: Overexpression of Snail in CRC cells induced an EMT phenotype with elevated expression of vimentin and reduced expression of E-cadherin. Snail-induced EMT did not alter cell proliferation but showed enhanced cell motility, in which Snail-expressing cells were 5- to 6-fold more migratory than the control cells. Snail also promoted the CSC-like phenotype demonstrated by increased expression of the CSC markers CD133. The aldefluor positive cell population in the Snail-expressing cells was increased ∼4 fold. Moreover, the Snail-expressing CRC cells showed increased chemoresistance to 5FU by 50%. Conclusion. High level of Snail expression confers the EMT and CSC phenotype in CRC cells, which enhanced cancer cell invasion and chemoresistance. Our data suggest that Snail may be a potential therapeutic target in metastatic colorectal cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2300.