SOX1 down-regulates β-catenin and reverses malignant phenotype in nasopharyngeal carcinoma

Background: Aberrant activation of the Wnt/beta-catenin signaling pathway is an important factor in the development of nasopharyngeal carcinoma (NPC). Previous studies have demonstrated that the developmental gene sex-determining region Y (SRY)-box 1 (SOX1) inhibits cervical and liver tumorigenesis by interfering with the Wnt/beta-catenin signaling pathway. However, the role of SOX1 in NPC remains unclear. This study investigates the function of SOX1 in NPC pathogenesis. Results: Down-regulation of SOX1 was detected in NPC cell lines and tissues. Besides, quantitative methylation-specific polymerase chain reaction revealed that SOX1 promoter was hypermethylated in NPC cell lines. Ectopic expression of SOX1 in NPC cells suppressed colony formation, proliferation and migration in vitro and impaired tumor growth in nude mice. Restoration of SOX1 expression significantly reduced epithelial-mesenchymal transition, enhanced cell differentiation and induced cellular senescence. Conversely, transient knockdown of SOX1 by siRNA in these cells partially restored cell proliferation and colony formation. Notably, SOX1 was found to physically interact with beta-catenin and reduce its expression independent of proteasomal activity, leading to inhibition of Wnt/beta-catenin signaling and decreased expression of downstream target genes. Conclusions: SOX1 decreases the expression of beta-catenin in a proteasome-independent manner and reverses the malignant phenotype in NPC cells.