ALDH1A1 Maintains The ESCC Cells Stemness By Activating The AKT Signal Pathway And Interacting With β-catenin

Objective: To investigate the molecular mechanism of ALDH1A1 in maintaining the properties of CSCs as well as the relationship between the expression level of Syndecan-1 and clinicopathological features and prognosis in patients with ESCC.Methods: ALDH1A1 immunohistochemistry was performed in esophageal squamous cell carcinoma(ESCC)tissues,Western Blot 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 ALDH1A1 and β-catenin.Results: ALDH1A1 is increased in ESCC and serves as a prognostic factor,also,its 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.Conclusions: We find a novel function of ALDH1A1,which is to maintain CSCs properties in ESCC by positively regulating the expression of upstream molecules AKT1 and β-catenin,and interacting with β-catenin.