SOD2 is a C-myc target gene that promotes the migration and invasion of tongue squamous cell carcinoma involving cancer stem-like cells
SOD2 is a C-myc target gene that promotes the migration and invasion of tongue squamous cell carcinoma involving cancer stem-like cells
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SOD2是C-myc靶基因，可促进涉及癌症干细胞样细胞的舌鳞状细胞癌的迁移和侵袭。
DOI：
10.1016/j.biocel.2014.12.022
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发表时间：
2015-03-01
影响因子：
4
通讯作者：
Wang, Anxun
中科院分区：
文献类型：
--
作者：
Liu, Zhonghua;He, Qianting;Wang, Anxun
我们的前期研究表明锰超氧化物歧化酶（SOD 2）参与舌鳞状细胞癌（TSCC）的迁移和侵袭。本研究的目的是进一步阐明SOD 2在TSCC迁移和侵袭中的作用机制。侧群（SP）细胞用作癌症干细胞样细胞，并通过球体和集落形成测定以及干细胞标志物（Bmi 1、Nanog和ABCG 2）的表达进一步评估。我们发现，与UM 2细胞（SOD 2表达、迁移和侵袭能力降低）相比，UM 1细胞（SOD 2表达、迁移和侵袭能力增加的TSCC细胞）具有更高比例的SP细胞、球体和集落形成，并表达更高水平的干细胞标志物。与非SP细胞相比，SP细胞的SOD 2表达以及迁移和侵袭能力增强。在UM 1细胞或SP细胞中敲低SOD 2抑制了细胞的迁移和侵袭能力，减少了球体和集落形成以及干细胞标志物的表达。通过染色质免疫沉淀和荧光素酶测定证明了C-myc蛋白与SOD 2启动子的直接结合。在UM 1细胞中敲低C-myc抑制SOD 2表达以及迁移和侵袭能力。我们的研究结果表明，肿瘤干细胞样细胞在TSCC的迁移和侵袭中起着重要作用。SOD 2是C-myc的直接靶基因，C-myc-SOD 2介导的TSCC迁移和侵袭涉及癌干细胞样细胞。(C)2015爱思唯尔有限公司版权所有。
Our previous studies revealed that manganese superoxide dismutase (SOD2) contributes to the migration and invasion of tongue squamous cell carcinoma (TSCC). The purpose of the current study was to further clarify the mechanisms of SOD2 in the migration and invasion of TSCC. Side population (SP) cells were used as cancer stem-like cells and further assessed by sphere and colony formation assays, and the expression of stem cell markers (Bmi1, Nanog and ABCG2). We found that UM1 cells (TSCC cells with increased SOD2 expression, migration and invasion abilities) possessed a higher proportion of SP cells, sphere and colony formation, and expressed a higher level of stem cell markers compared to UM2 cells (reduced SOD2 expression, migration and invasion abilities). SOD2 expression as well as migration and invasion abilities were enhanced in SP cells compared to non-SP cells. Knockdown of SOD2 in UM1 cells or SP cells inhibited the migration and invasion abilities, reduced sphere and colony formation, and the expression of stem cell markers. Direct binding of the C-myc protein to the SOD2 promoter was demonstrated by chromatin immunoprecipitation and luciferase assays. Knockdown of C-myc in UM1 cells inhibited SOD2 expression as well as migration and invasion abilities. Our results indicate that cancer stem-like cells play an important role in the migration and invasion of TSCC. SOD2 is a direct target gene of C-myc and C-myc-SOD2-mediated migration and invasion of TSCC involve cancer stem-like cells. (C) 2015 Elsevier Ltd. All rights reserved.