DKK1 maintained cancer stem-like properties of esophageal carcinoma cells via ALDH1A1/SOX2 axis.

Dickkopf-1 (DKK1) has been reported as a key regulator in the progression of esophageal carcinoma (EC). Aldehyde dehydrogenase 1A1 (ALDH1A1) possesses stem-like properties and predicts patient outcome in several cancers. However, whether DKK1 regulates cancer stem-like properties of EC cells through modulating ALDH1A1 activity remains unclear. In this study, we found that DKK1 knockdown significantly reduced cell proliferation, colony formation and CK18 expression. Additionally, knockdown of DKK1 also decreased the expression of ALDH1A1 involved in a c-Jun-dependent manner through a pathway consisting of p38/JNK/c-Jun pathway. Furthermore, the downregulation of ALDH1A1 gene expression in Eca109 resulted in decreased expression of cancer stem cell-associated markers SOX2, Bmi1 and vimentin. Therefore, our results demonstrated that DKK1 maintained cancer stem-like properties of EC cells via ALDH1A1/SOX2 axis. DKK1 may act as a therapeutic target for the treatment of EC. IJCEP