OCT4 regulates epithelial-mesenchymal transition and its knockdown inhibits colorectal cancer cell migration and invasion

• DOI: 10.3892/or.2012.2086
• Publication Date: 2012-10-17T08:18:34Z
• Authors: XINZHENG DAI; JING GE; XUEHAO WANG; XIAOFENG QIAN; CHUANYONG ZHANG; XIANGCHENG LI
• Keywords: 0301 basic medicine; 0303 health sciences; Epithelial-Mesenchymal Transition; Blotting, Western; Liver Neoplasms; Fluorescent Antibody Technique; Mice, Nude; Apoptosis; Prognosis; 3. Good health; Immunoenzyme Techniques; Mice; 03 medical and health sciences; Cell Movement; Biomarkers, Tumor; Cell Adhesion; Animals; Humans; Female; Neoplasm Invasiveness; Colorectal Neoplasms; Octamer Transcription Factor-3; Cell Proliferation; Neoplasm Staging

Octamer-binding transcription factor 4 (OCT4) has been implicated in cancer metastasis. In this study, we investigated whether OCT4 promotes colorectal cancer (CRC) metastasis through the epithelial-mesenchymal transition (EMT) process. We designed our experiment as a loss-of-function study. Western blot analysis was used to measure the extent and stability of OCT4 knockdown. We evaluated the metastatic phenotype of OCT4-silenced SW620 cells using standard migration and invasion assays in vitro and the commonly used mouse model for experimental metastases in vivo. We found that OCT4 knockdown inhibited colorectal cancer cell motility and invasion (in vitro) and decreased hepatic colonization (in vivo). It also induced changes in EMT characteristic cell morphology and marker gene expression. In addition, its knockdown decreased WNT pathway activity. Finally, in human primary colorectal cancers, the frequency of upregulated OCT4 expression in cases with liver metastasis was statistically higher than that in cases without liver metastasis. These results indicate that OCT4 may contribute to CRC cell metastasis through EMT and serves as a promising biomarker for identifying CRC patients at high risk for liver metastases.