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

Oncol Rep. 2013 Jan;29(1):155-60. doi: 10.3892/or.2012.2086. Epub 2012 Oct 17.

Abstract

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.

MeSH terms

  • Animals
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Blotting, Western
  • Cell Adhesion
  • Cell Movement*
  • Cell Proliferation
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • Epithelial-Mesenchymal Transition*
  • Female
  • Fluorescent Antibody Technique
  • Humans
  • Immunoenzyme Techniques
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / secondary*
  • Mice
  • Mice, Nude
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Octamer Transcription Factor-3 / antagonists & inhibitors
  • Octamer Transcription Factor-3 / genetics
  • Octamer Transcription Factor-3 / metabolism*
  • Prognosis
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured

Substances

  • Biomarkers, Tumor
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • RNA, Messenger
  • RNA, Small Interfering