Manganese superoxide dismutase induces migration and invasion of tongue squamous cell carcinoma via H₂O₂-dependent Snail signaling

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• 作者：Zhonghua Liu^a ; ¹ ; Su Li^c ; ¹ ; Yuchen Cai^c ; Anxun Wang^a ; ^{anxunwang@yahoo.com} ; Qianting He^a ; Chaoxu Zheng^b ; Tingting Zhao^a ; Xueqiang Ding^a ; Xiaofeng Zhou^d ; ^e ; ^f
• 关键词：SOD2 ; manganese superoxide dismutase ; TSCC ; tongue squamous cell carcinoma ; MMP ; matrix metalloproteinase ; ERK ; extracellular signal-regulated kinase ; pERK ; phosphorylated extracellular signal-regulated kinase ; shRNA ; short hairpin RNA ; SACC ; salivary ade
• 刊名：Free Radical Biology and Medicine
• 出版年：2012
• 期刊代码：105_08915849
• 类别：med
• 出版时间：1 July, 2012
• 卷：53
• 期：1
• 页码：44-50
• 文件大小：1094 K

摘要

Our previous studies had revealed that the dysregulation of manganese superoxide dismutase (SOD2) expression was a frequent event in tongue squamous cell carcinoma (TSCC) and may be associated with enhanced metastatic potential. To further evaluate the mechanism of SOD2-mediated metastasis in TSCC, TSCC cell lines with different metastatic potentials (i.e., the highly metastatic UM1 line and the UM2 line, which displays fewer metastases) were used. Compared to UM2 cells, UM1 cells exhibited significantly higher SOD2 activity and intracellular H₂O₂; higher protein levels of Snail, MMP1, and pERK1/2; lower protein levels of E-cadherin; and no difference in catalase activity. Upon knockdown of SOD2 by RNA interference, UM1 cells displayed significantly reduced migration and invasion abilities; reduced activities of SOD2; lower intracellular H₂O₂; decreased protein levels of Snail, MMP1, and pERK1/2; and increased protein levels of E-cadherin. The migration and invasion abilities of UM2 and SOD2 shRNA-transfected UM1 cells were enhanced by H₂O₂ treatment and accompanied by increased protein levels of Snail, MMP1, and pERK1/2 and decreased protein levels of E-cadherin. Moreover the migration and invasion abilities of UM1 cells were decreased after catalase treatment. Thus, we conclude that the SOD2-dependent production of H₂O₂ contributes to both the migration and the invasion of TSCC via the Snail signaling pathway, through increased Snail, MMP1, and pERK1/2 protein levels and the repression of the E-cadherin protein.