期刊论文详细信息
Cancer Medicine
Overexpression of Snail induces epithelial–mesenchymal transition and a cancer stem cell–like phenotype in human colorectal cancer cells
Fan Fan1  Shaija Samuel1  Kurt W. Evans2  Jia Lu1  Ling Xia1  Yunfei Zhou1  Eric Sceusi3  Federico Tozzi3  Xiang-Cang Ye1  Sendurai A. Mani2 
[1] Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas;Department of Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas;Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
关键词: Cancer stem cells;    colorectal cancer;    EMT;    migration;    Snail;   
DOI  :  10.1002/cam4.4
来源: Wiley
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【 摘 要 】

Abstract

Epithelial–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 was shown to be associated with the cancer stem cell (CSC) phenotype in breast cancer. Snail is a transcription factor that mediates EMT in a number of tumor types, including colorectal cancer (CRC). Our study was done to determine the role of Snail in mediating EMT and CSC function in CRC. Human CRC specimens were stained for Snail expression, and human CRC cell lines were transduced with a retroviral Snail construct or vector control. Cell proliferation and chemosensitivity to oxaliplatin of the infected cells were determined by the MTT (colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Migration and invasion were determined in vitro using modified Boyden chamber assays. EMT and putative CSC markers were analyzed using Western blotting. Intravenous injection of tumor cells was done to evaluate their metastatic potential in mice. Snail was overexpressed in human CRC surgical specimens. This overexpression induced EMT and a CSC-like phenotype in human CRC cells and enhanced cell migration and invasion (< 0.002 vs. control). Snail overexpression also led to an increase in metastasis formation in vivo (< 0.002 vs. control). Furthermore, the Snail-overexpressing CRC cells were more chemoresistant to oxaliplatin than control cells. Increased Snail expression induces EMT and the CSC-like phenotype in CRC cells, which enhance cancer cell invasion and chemoresistance. Thus, Snail is a potential therapeutic target in metastatic CRC.

【 授权许可】

CC BY-NC   
© 2012 The Authors. Cancer Medicine published by Blackwell Publishing Ltd.

Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

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