ALDH1A1 maintains the cancer stem-like cells properties of esophageal squamous cell carcinoma by activating the AKT signal pathway and interacting with β-catenin.

Aldehyde dehydrogenase 1A1 (ALDH1A1) is a marker of cancer stem-like cells (CSCs), but knowledge about the molecular mechanism of ALDH1A1 in maintaining the properties of CSCs remains limited. ALDH1A1 immunohistochemistry was performed in esophageal squamous cell carcinoma (ESCC) tissues, Western blotting was used to detect relationship between ALDH1A1 and AKT or β-catenin. Subcutaneous transplantation of tumors and drug resistance, spherogenesis experiments were used to test the ESCC cell stemness. Co-IP and confocal were used to detected the co-localization of LADH1A1 and β-catenin. ALDH1A1 expression maintained the CSC properties of ESCC cells. It enhanced the chemo-resistance ability, clonogenicity, and spherogenesis in vitro and tumorigenicity in vivo. High ALDH1A1 expression is an adverse prognostic factor of ESCC patients. Small-molecule inhibitor NCT-501 down-regulates ALDH1A1 expression and inhibits the AKT-β-catenin signaling pathway. ALDH1A1 overexpression activates the AKT signaling pathway. ALDH1A1 interacts with β-catenin, co-localization in KYS-510 cells.