Yancan Liang1,2, Jiuyang Jiao1,2, Lizhong Liang3, Jin Zhang4, Yingjuan Lu1,2, Hongliang Xie5, Qixiang Liang6, Di Wan1,2, Liming Duan1,2, You Wu1,2, Bin Zhang1,2. 1. Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. 2. Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangzhou Higher Education Institutes, Sun Yat-sen University, Guangzhou, China. 3. Department of ENT, Head and Neck, Oral and Maxillofacial Surgery, Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China. 4. Department of Internal Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. 5. Department of Stomatology, Shenzhen People's Hospital, Shenzhen, China. 6. Department of Stomatology, the third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Abstract
BACKGROUND: Tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) 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 TRAF6 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 TRAF6. Downstream proteins expression was explored when TRAF6 was knockdown by siRNA. RESULTS: The results show that TRAF6 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 TRAF6 can attenuate the promotion effect of SACC cell invasion induced by TGF-β. Western blot results also showed that silencing TRAF6 expression can inhibit the activation of SMAD2, SMAD3, ERK, p38, and JNK induced by TGF-β in SACC cells. CONCLUSION: These data suggested that TRAF6 regulates TGF-β-mediated SACC progression through SMAD2/3-ERK-p38-JNK cascades.
BACKGROUND:Tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) 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 TRAF6 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 TRAF6. Downstream proteins expression was explored when TRAF6 was knockdown by siRNA. RESULTS: The results show that TRAF6 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 TRAF6 can attenuate the promotion effect of SACC cell invasion induced by TGF-β. Western blot results also showed that silencing TRAF6 expression can inhibit the activation of SMAD2, SMAD3, ERK, p38, and JNK induced by TGF-β in SACC cells. CONCLUSION: These data suggested that TRAF6 regulates TGF-β-mediated SACC progression through SMAD2/3-ERK-p38-JNK cascades.