ALBERT

Description: Cancer stem cells (CSCs) play a key role in tumor radiotherapy and chemotherapy resistance, relapse, and metastasis, and are primarily maintained in a resting state in vivo . The failure of conventional therapies to target CSCs is the main cause of treatment failure. The discovery of CSCs in nasopharyngeal carcinoma (NPC) tumors is becoming more prevalent; however, the understanding of the mechanisms underlying the maintenance of tumor stemness is still limited. We previously cloned NOR1, a tumor suppressor gene downregulated in NPC cell lines and tissues. In this study, we demonstrate that Wnt/β-catenin and ALDH1A1 form a signal circuit and that NOR1 antagonizes the tumor stem cell-like phenotype in NPC cell lines: the ectopic overexpression of NOR1 reduced β-catenin and ALDH1A1 expression; β-catenin/TCF4 targeted the regulation of ALDH1A1 transcription in NPC cells; silencing ALDH1A1 reduced AKT (total and phosphorylated) and GSK-3β (phosphorylated) expression; and eventually feedback decreased β-catenin expression levels. We also found that NOR1 expression decreased cancer stem-like cell properties of NPC cells, reduced their ability to form tumor spheroids in vitro , reduced tumorigenicity in nude mice in vivo , and increased sensitivity to chemotherapy agents. Taken together, our findings illustrated a new function of NOR1 that suppresses cancer stem-like cell properties in tumor cells by inhibiting the AKT-GSK-3β-Wnt/β-catenin-ALDH1A1 signal circuit. The study suggests that NOR1 deletion expression in NPC cells may be a potential molecular target for cancer stem cell therapy. This article is protected by copyright. All rights reserved