OCT3 and SOX2 promote the transformation of Barrett's esophagus to adenocarcinoma by regulating the formation of tumor stem cells

Barrett's esophagus (BE) is a type of precancerosis and a key risk factor for esophagus adenocarcinoma (EAC). Tumor stem cells may be the source for BE transforming to EAC. Octamer transcription factor-3/4 (OCT3/4) and SOX2 are the main transcriptional controlling factors and markers of tumor stem cells. In the present study, we observed that the expressions of OCT3/4, SOX2, TCL1 and AKT1 in BE were elevated compared to normal esophagus but were decreased compared to EAC. Moreover, we isolated a few stem-like cells in OE33 cells which showed similar biological behavior to tumor stem cells. Notably, we found that downregulation of OCT3/4 expression by siRNA inhibited the ability of clone formation and invasion of OE33 cells, and decreased the formation of side population cells and slow cycle cells. Therefore, we concluded that OCT3/4 and SOX2 play a critical role in the transformation of BE to EAC by regulating the formation of tumor stem cells and the TCL1/AKT1 pathway.