Wang Wei, He Shujin, Zhang Renya, Peng Jie, Guo Daolu, Zhang Jinguo, Xiang Bo, Li Lei
Department of Pathology, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong 272029, China.
Department of Pathology, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong 272029, China.
Biomed Pharmacother. 2020 May;125:109940. doi: 10.1016/j.biopha.2020.109940. Epub 2020 Feb 7.
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.
乙醛脱氢酶1A1（ALDH1A1）是癌症干细胞样细胞（CSCs）的标志物，但关于ALDH1A1维持CSCs特性的分子机制的了解仍然有限。在食管鳞状细胞癌（ESCC）组织中进行了ALDH1A1免疫组织化学检测，采用蛋白质印迹法检测ALDH1A1与AKT或β-连环蛋白之间的关系。通过肿瘤皮下移植和耐药性、成球实验来检测ESCC细胞的干性。采用免疫共沉淀和共聚焦技术检测LADH1A1与β-连环蛋白的共定位。ALDH1A1的表达维持了ESCC细胞的CSC特性。它增强了体外的化疗耐药能力、克隆形成能力和成球能力以及体内的致瘤性。高ALDH1A1表达是ESCC患者的不良预后因素。小分子抑制剂NCT-501下调ALDH1A1表达并抑制AKT-β-连环蛋白信号通路。ALDH1A1过表达激活AKT信号通路。ALDH1A1与β-连环蛋白相互作用，在KYS-510细胞中共定位。
