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.
Previous study demonstrated that hypermethylation of NOR1 promoter was observed in NPC and hematological malignancies, which has been believed to be the main epigenetic cause for NOR1 silencing in these cancers.
Expression of oxidored nitro domain-containing protein 1(NOR1) impairs nasopharyngeal carcinoma cells adaptation to hypoxia and inhibits PDK1 expression.
Previous studies have reported that oxidored-nitro domain containing protein 1 (NOR1) is a novel tumor suppressor gene identified in various types of cancer, such as nasopharyngeal carcinoma and cervical cancer.
Therefore, NOR1 is an important tumor suppressor gene associated with NPC and CCA and may play antitumor roles by inhibiting proliferation, preventing colony formation, and promoting the apoptosis of tumor cells via the mitochondrial-dependent apoptotic pathway.
These data shed light on the selectivity of potential physiological functions of NOR1 and provides an indispensable reference to the carcinogenesis process of NPC and to identify or validate tissue-specific drug targets.