Tumor necrosis factor receptor‐associated factor 6 mediated the promotion of salivary adenoid cystic carcinoma progression through Smad‐p38‐JNK signaling pathway induced by TGF‐β

Background Tumor necrosis factor ( TNF ) receptor‐associated factor 6 ( TRAF 6) has been proved to play an important role in tumorigenesis, invasion, and metastasis. However, its precise role salivary adenoid cystic carcinoma ( SACC ) has not been determined. The aim of this study was to explore the role of TRAF 6 in SACC including invasion and metastasis of SACC cells. Materials and methods Immunohistochemistry and quantitative real‐time PCR were performed in SACC tissues paired with their adjacent normal tissues to analyze the expression of TRAF 6. Downstream proteins expression was explored when TRAF 6 was knockdown by si RNA . Results The results show that TRAF 6 is upregulated in SACC samples, especially in SACC with metastasis, which is closely correlated with an aggressive phenotype ( P = .0073) and shorter life survival span ( P = .0061) in SACC patients. Knockdown of TRAF 6 can attenuate the promotion effect of SACC cell invasion induced by TGF ‐β. Western blot results also showed that silencing TRAF 6 expression can inhibit the activation of SMAD 2, SMAD 3, ERK , p38, and JNK induced by TGF ‐β in SACC cells. Conclusion These data suggested that TRAF 6 regulates TGF ‐β‐mediated SACC progression through SMAD 2/3‐ ERK ‐p38‐ JNK cascades.