Forkhead Box Protein M1 Promotes Nasopharyngeal Carcinoma Cell Tumorigenesis Possibly via the Wnt/β-Catenin Signaling Pathway.

BACKGROUND Forkhead box protein M1 (FoxM1) is an important transcription factor involved in the development and progression of various malignancies. However, its role in nasopharyngeal carcinoma (NPC) remains largely unknown. This study aimed to assess the effect of FoxM1 on NPC cell tumorigenesis as well as the underlying mechanism. MATERIAL AND METHODS NPC cell lines CNE-1 and CNE-2 were treated with vehicle and FoxM1 inhibitor thiostrepton or transfected with small interfering RNA. CCK-8 assay, flow cytometric assay, and Hoechst 33258 staining were performed to assess the viability, apoptosis and nuclear morphological impairment, and cell cycle, respectively. The expression of apoptosis-related caspase-3 and caspase-9 was detected by western blot analysis The tumor growth in the mouse xenograft model of NPC treated with thiostrepton or control was assessed. The expression of Wnt/ß-catenin signaling proteins p27, FoxM1, S phase kinase-associated protein 2 (SKP2), and Cyclin D1 were determined both in cells and xenograft tissues by western blot analysis. RESULTS Inhibition of FoxM1 by thiostrepton significantly suppressed NPC cell viability, induced apoptosis, increased cell cycle arrest, impaired nuclear morphology, and reduced NPC cell-derived tumor xenograft growth. Mechanistically, inhibition or knockdown of FoxM1 inactivated the Wnt/ß-catenin signaling pathway, as demonstrated by altered expression of Wnt/ß-catenin signaling-related genes, including p27, SKP2, and cyclin D1, in both NPC cells and xenograft tissues. CONCLUSIONS We identified FoxM1 as a novel regulator of NPC cell tumorigenesis in vitro and in vivo. Targeting FoxM1 could be a promising therapeutic strategy against NPC.