In vitro spontaneous MET-EMT model confers distinct cancer phenotypes and provides clues for differential epigenetic regulation.

Abstract

Abstract Background Epithelial-mesenchymal plasticity is known to be involved in cancer metasis and chemotherapy resistance. However, molecular mechanisms of transitions between these cellular states is not well understood and good representative models that mimic natural transitions are still needed. In this study, spontaneously differentiating colon cancer cell line, HT-29, was used to develop an MET-EMT model. Methods and results Cells were first characterized according to their protein levels of epithelial and mesenchymal markers, so that the accuracy of the model has been proven. In order to elucidate the plastic nature of EMT, changes in the amounts of Polycomb group proteins were analyzed. Further characterization is achieved by comparing drug resistance, proliferation and colony formation ability. It was found that the amount of CBX-7 increased in epithelial cells, the amount of EZH1, EZH2 and CBX-8 increased in mesenchymal cells compared to epithelial cells. In addition, it was determined that epithelial cells were more sensitive to oxaliplatin and 5-FU, their division rate was lower than mesenchymal cells, and their ability to form spheroids was also lower. Conclusion This study provides a useful model for the study of epithelial mesenchymal plasticity in which the same cell line is used for reversible transitions whithout any chemical induction.