Silencing SOX2 induced mesenchymal-epithelial transition and its expression predicts liver and lymph node metastasis of CRC patients

Xu Han; Xuefeng Fang; Xiaoyan Lou; Dasong Hua; Wenchao Ding; Gregory Foltz; Leroy Hood; Ying Yuan; Biaoyang Lin

doi:10.1371/journal.pone.0041335

Silencing SOX2 induced mesenchymal-epithelial transition and its expression predicts liver and lymph node metastasis of CRC patients

PLoS One. 2012;7(8):e41335. doi: 10.1371/journal.pone.0041335. Epub 2012 Aug 17.

Authors

Xu Han¹, Xuefeng Fang, Xiaoyan Lou, Dasong Hua, Wenchao Ding, Gregory Foltz, Leroy Hood, Ying Yuan, Biaoyang Lin

Affiliation

¹ Systems Biology Division, Zhejiang-California International Nanosystems Institute, Zhejiang University, Hangzhou, Zhejiang, China.

Abstract

SOX2 is an important stem cell marker and plays important roles in development and carcinogenesis. However, the role of SOX2 in Epithelial-Mesenchymal Transition has not been investigated. We demonstrated, for the first time, that SOX2 is involved in the Epithelial-Mesenchymal Transition (EMT) process as knock downof SOX2 in colorectal cancer (CRC) SW620 cells induced a Mesenchymal-Epithelial Transition (MET) process with recognized changes in the expression of key genes involved in the EMT process including E-cadherin and vimentin. In addition, we provided a link between SOX2 activity and the WNT pathway by showing that knock down of SOX2 reduced the WNT pathway activity in colorectal cancer (CRC) cells. We further demonstrated that SOX2 is involved in cell migration and invasion in vitro and in metastasis in vivo for CRC cells, and that the process might be mediated through the MMP2 activity. Finally, an IHC analysis of 44 cases of colorectal cancer patients suggested that SOX2 is a prognosis marker for metastasis of colorectal cancers.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line, Tumor
Cell Movement / genetics
Colorectal Neoplasms / genetics
Colorectal Neoplasms / pathology*
Down-Regulation / genetics
Epithelial-Mesenchymal Transition / genetics*
Female
Gene Expression Regulation, Neoplastic / genetics*
Gene Silencing*
Humans
Liver Neoplasms / secondary*
Lymphatic Metastasis
Lymphoid Enhancer-Binding Factor 1 / metabolism
Matrix Metalloproteinase 2 / metabolism
Mice
Neoplasm Invasiveness
SOXB1 Transcription Factors / deficiency*
SOXB1 Transcription Factors / genetics*
Signal Transduction / genetics
TCF Transcription Factors / metabolism
beta Catenin / metabolism

Substances

Lymphoid Enhancer-Binding Factor 1
SOX2 protein, human
SOXB1 Transcription Factors
TCF Transcription Factors
beta Catenin
Matrix Metalloproteinase 2

Grants and funding

Supported by grants to BL from the Ministry of Science and Technology of China [grant 2006AA02A303, 2006AA02Z4A2, 2006DFA32950 and 2007DFC30360], and grant to XF from the National Natural Science Foundation of China (No. 81101580). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.