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Biomed Pharmacother ; 125: 109940, 2020 May.
Article in English | MEDLINE | ID: mdl-32044720

ABSTRACT

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 ß-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 ß-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-ß-catenin signaling pathway. ALDH1A1 overexpression activates the AKT signaling pathway. ALDH1A1 interacts with ß-catenin, co-localization in KYS-510 cells.


Subject(s)
Aldehyde Dehydrogenase 1 Family/genetics , Esophageal Neoplasms/pathology , Esophageal Squamous Cell Carcinoma/pathology , Neoplastic Stem Cells/metabolism , Retinal Dehydrogenase/genetics , Adult , Aged , Aged, 80 and over , Animals , Esophageal Neoplasms/genetics , Esophageal Squamous Cell Carcinoma/genetics , Female , Gene Expression Regulation, Neoplastic , Humans , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Middle Aged , Piperazines/pharmacology , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , Theophylline/pharmacology , beta Catenin/metabolism
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