Overexpression of Snail induces epithelial–mesenchymal transition and a cancer stem cell–like phenotype in human colorectal cancer cells

Cancer Medicine

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

【 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 (P < 0.002 vs. control). Snail overexpression also led to an increase in metastasis formation in vivo (P < 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.

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