Silencing SOX2 induced mesenchymal-epithelial transition and its expression predicts liver and lymph node metastasis of CRC patients.
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.
Systems Biology Division, Zhejiang-California International Nanosystems Institute, Zhejiang University, Hangzhou, Zhejiang, China.
Xu
X
Han
Xuefeng
X
Fang
Xiaoyan
X
Lou
Dasong
D
Hua
Wenchao
W
Ding
Gregory
G
Foltz
Leroy
L
Hood
Ying
Y
Yuan
Biaoyang
B
Lin
D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology*; D015536:Down-Regulation / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D020868:Gene Silencing; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary*; D008207:Lymphatic Metastasis; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D009361:Neoplasm Invasiveness; D055748:SOXB1 Transcription Factors / Q000172:deficiency* / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D051820:TCF Transcription Factors / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
D051821:Lymphoid Enhancer-Binding Factor 1; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D051820:TCF Transcription Factors; D051176:beta Catenin; D020778:Matrix Metalloproteinase 2