SOX1 down-regulates [beta]-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...

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Bibliographic Details
Published in:Molecular cancer 2014-11, Vol.13
Main Authors: Guan, Zhong, Zhang, Jialiang, Wang, Jing, Wang, Hefei, Zheng, Feimeng, Peng, Jieren, Xu, Yaodong, Yan, Min, Liu, Bing, Cui, Bai, Huang, Ying, Liu, Quentin
Format: Article
Language:English
Subjects:
Experiments
Genes
Genotype & phenotype
Laboratories
Liver
Liver cancer
Otolaryngology
Physiological aspects
Polymerase chain reaction
Proteins
Software
Stem cells
Transcription factors
Tumorigenesis
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Summary: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. Keywords: SOX1, [beta]-catenin, Methylation, Differentiation, NPC
ISSN:1476-4598
1476-4598
DOI:10.1186/1476-4598-13-257