Oral squamous cell carcinoma (OSCC) ranks as the fifth most common cancer worldwide with poor prognosis. Recently, tumor necrosis factor receptor-associated factor 4 (TRAF4) has attracted increasing attenuation due to its overexpression in certain cancers. However, its function and underlying mechanism in OSCC remains elusive. In this study, the high expression of TRAF4 mRNA and protein levels was noted in OSCC cell lines. Its overexpression with pcDNA3.1-TRAF4 vector transfection dramatically promoted cell proliferation and inhibited cell apoptosis, indicating a pivotal role of TRAF4 in OSCC cell growth. Simultaneously, TRAF4 elevation also increased cell invasion and migration. Mechanism analysis confirmed that TRAF4 up-regulation induced the expression of β-catenin and the downstream target molecules of cyclinD1, c-myc, Bcl-2, MMP-9 and MMP-2, indicating that TRAF4 could induce the activation of Wnt/β-catenin pathway. After pretreatment with β-catenin siRNA, the pathway was remarkably silenced. Simultaneously, cell growth, invasion and migration induced by TRAF4 were strikingly abrogated, suggesting that TRAF4 may promote OSCC cell growth, invasion and migration by Wnt/β-catenin pathway. Together, this study confirmed that TRAF4 acts as an oncogene for the development and progression of OSCC. Therefore, our study may support a promising therapeutic target for the treatment of OSCC.
Keywords: Oral squamous cell carcinoma; TRAF4; Wnt/β-catenin pathway; cell growth; cell invasion; cell migration.