Sex-determining region Y-box protein 3 induces epithelial-mesenchymal transition in osteosarcoma cells via transcriptional activation of Snail1

Abstract

BackgroundThe transcription factor sex-determining region Y-box protein 3 (SOX3) plays important roles in various types of cancer. However, its expression and function have not yet been elucidated in osteosarcoma (OS).MethodsThe expression levels of SOX3 in OS tissues and OS cell lines were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. The effects of SOX3 expression on OS cell biological traits were investigated by overexpressing and downregulating SOX3 protein. The expression of epithelial-mesenchymal transition (EMT) markers and transcription factors associated with EMT (EMT-TFs), were detected simultaneously. The mechanism underlying SOX3-mediated Snail1 expression was further investigated.ResultsSOX3 was upregulated in human OS tissues. SOX3 overexpression promoted the EMT, migration and invasion in OS cells. The downregulation of SOX3 resulted in opposing effects. Furthermore, SOX3 upregulation enhanced the expression of the transcriptional repressor Snail1 by binding to its promoter region. Additionally, a positive correlation among the expression of SOX3, Snail1, and E-cadherin was demonstrated in human OS tissues.ConclusionsSOX3 promotes migration, invasiveness, and EMT in OS cells via transcriptional activation of Snail1 expression, suggesting that SOX3 is a novel regulator of EMT in OS and may serve as a therapeutic target for the treatment of OS metastasis.

Tspan9 Induces EMT and Promotes Osteosarcoma Metastasis via Activating FAK-Ras-ERK1/2 Pathway

“…Epithelial-mesenchymal transition (EMT) is a process integral to metastatic progression wherein tumor cells shed their epithelial-like properties and instead acquire more motile mesenchymal characteristics. EMT induction is critical to malignant cell dissemination in the context of OS progression (18,19), and EMT-regulating transcription factors including the zinc-finger-binding transcription factors Snai1 and Slug, zinc finger E−box −binding homeobox 1 (ZEB1), and the Twist1 and Twist2 basic helix-loop-helix (bHLH) factors have been shown to control this process in OS cells and to regulate associated metastasis (20)(21)(22). Integrins, which are heterodimeric receptors with a and b subunits that bind to the extracellular matrix, also regulate tumor malignancy.…”

Multi-Omics Characterization of the Spontaneous Mesenchymal–Epithelial Transition in the PMC42 Breast Cancer Cell Lines

“…Some of the allelic heterogeneous mutations detected in PMC42-LA have also been associated with EMT drivers or markers; we identified novel mutations in GSN (R397W), WNT1 (T363K), SNAI2 (K188N), ITGA4 (R565W), SOX3 (R22P) and NID2 (G426E) (Supplementary Table S7). SNAI2-null mice are reported to have retarded epithelial migration rates [79], and SOX3 has been implicated in the malignant behaviour of glioblastoma [80], EMT, and in the promotion of migration and invasion of osteosarcoma cells [81,82]. A N161K mutation in SOX3 was found associated with progression of SCLC along with other mutated SOX members [83].…”

Clinical Correlation of Transcription Factor SOX3 in Cancer: Unveiling Its Role in Tumorigenesis

“…Qiu et al [47] identified SOX3 as a metastasis-associated gene in OS, highlighting its mechanistic connection with the TFs SNAIL1 and MET. SOX3 was overexpressed in 42 cases of human OS tissues in comparison with non-tumor samples.…”