Manganese superoxide dismutase induces migration and invasion of tongue squamous cell carcinoma via H2O2-dependent Snail signaling.
Manganese superoxide dismutase induces migration and invasion of tongue squamous cell carcinoma via H2O2-dependent Snail signaling.
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DOI：
10.1016/j.freeradbiomed.2012.04.031
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发表时间：
2012-07-01
影响因子：
7.4
通讯作者：
Zhou, Xiaofeng
中科院分区：
文献类型：
--
作者：
Liu, Zhonghua;Li, Su;Cai, Yuchen;Wang, Anxun;He, Qianting;Zheng, Chaoxu;Zhao, Tingting;Ding, Xueqiang;Zhou, Xiaofeng
我们以前的研究表明锰超氧化物歧化酶（SOD 2）表达失调是舌鳞状细胞癌（TSCC）的常见事件，并可能与转移潜能增强有关。为了进一步评估SOD 2介导的TSCC转移的机制，将具有不同转移潜能的TSCC细胞系（即，高转移性UM 1系和显示较少转移的UM 2系）。与UM 2细胞相比，UM 1细胞内SOD 2活性和H2 O2水平显著升高，Snail、MMP-1和pERK 1/2蛋白水平显著升高，E-cadtherin蛋白水平显著降低，而过氧化氢酶活性无显著差异。RNA干扰抑制SOD 2表达后，UM 1细胞迁移和侵袭能力明显降低，SOD 2活性降低，细胞内H2 O2水平降低，Snail、MMP-1和pERK 1/2蛋白水平降低，E-cadtherin蛋白水平升高。H2 O2处理后，转染UM 2和SOD 2 shRNA的UM 1细胞的迁移和侵袭能力增强，Snail、MMP-1和pERK 1/2蛋白水平升高，E-cadtherin蛋白水平降低。UM 1细胞经过氧化氢酶处理后，其迁移和侵袭能力明显降低。因此，我们的结论是，SOD 2依赖性生产的H2 O2有助于通过Snail信号通路，通过增加Snail，MMP-1和pERK 1/2蛋白水平，并抑制E-cadtherin蛋白的迁移和侵袭的TSCC。
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 potential (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, MMP-1 and pERK1/2, lower protein levels of E-cadtherin, and not difference of 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, MMP-1 and pERK1/2, and increased protein levels of E-cadtherin. Migration and invasion ability of UM2 and SOD2 shRNA-transfected UM1 cells were enhanced by H2O2 treatment and accompanied by increased protein levels of Snail, MMP-1 and pERK1/2, and decreased protein levels of E-cadtherin. Moreover the migration and invasion ability of UM1 cells were decreased after catalase treatment. Thus, we conclude that the SOD2-dependent production of H2O2 contributes to both the migration and invasion of TSCC via the Snail signaling pathway through increased Snail, MMP-1 and pERK1/2 protein levels, and the repression of the E-cadtherin protein.
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影响因子：
2.8
作者：
Hempel N;Carrico PM;Melendez JA
通讯作者：
Melendez JA
影响因子：
4.8
作者：
Ranganathan, AC;Nelson, KK;Melendez, JA
通讯作者：
Melendez, JA
影响因子：
11.2
作者：
Connor, Kip M.;Hempel, Nadine;Melendez, J. Andres
通讯作者：
Melendez, J. Andres
影响因子：
4
作者：
Joseph, Mathew J.;Dangi-Garimella, Surabbi;Munshi, Hidayatullah G.
通讯作者：
Munshi, Hidayatullah G.
氧化还原状态的改变伴随着人类转移性膀胱癌的进展。
影响因子：
7.4
作者：
Hempel, Nadine;Ye, Hanqing;Abessi, Bryan;Mian, Badar;Melendez, J. Andres
通讯作者：
Melendez, J. Andres