Investigation of the epigenetic changes during epithelial-mesenchymal transition of colon cancer cells

Colorectal cancer (CRC) is one of the most common malignant tumors worldwide. CRC is a type of cancer that is generally curable, but metastasis of the cancer adversely affects the course of the disease. An important biological process associated with cancer metastasis is epithelial mesenchymal transition (EMT). For this reason, elucidating the EMT-MET process is an important step towards elucidating metastasis, which is the most important cause of cancer deaths. Much evidence indicates that EMT in normal cells and tumor cells is regulated as an epigenetic process, not as a result of changes in DNA sequence. In this study, a new model that can spontaneously undergo MET and EMT was created using a colon cancer cell line HT-29. Three types of subpopulations, ancestral, epithelial, and mesenchymal, were obtained in the HT-29 MET-EMT cell model, and these subpopulations were characterized for epithelial mesenchymal markers, histone modifications, epigenetic regulators, drug resistance, and cell proliferation. It was observed that epithelial markers increased in epithelial cells and mesenchymal markers increased in mesenchymal and ancestral cells. In this MET-EMT model, while the suppressor histone sign increases in epithelial cells, the activating histone sign decreases. In addition, the protein amounts of EZH1, CBX-4, and CBX-7 has increased in epithelial cells, while the amounts of CBX-8 and EZH2 has decreased. For 5-fluorouracil and oxaliplatin in the MET-EMT model, higher resistance was observed in mesenchymal cells, although not statistically significant. Cell viability was much higher in the ancestral and mesenchymal groups than in the epithelial group. The study constitutes an important step towards elucidating the epigenetic mechanisms and identifying new treatment targets in colon cancer and the MET-EMT process. Keywords: Epigenetic, epithelial-mesenchymal transition, drug resistance, colon cancer, polycomb protein