Connexin 43 Reverses Malignant Phenotypes of Glioma Stem Cells by Modulating E-Cadherin

被引：99

作者：

Yu, Shi-Cang ^{[1
,2
]}

Xiao, Hua-Liang ^{[1
,2
]}

Jiang, Xue-Feng ^{[1
,2
]}

Wang, Qing-Liang ^{[1
,2
]}

Li, Yan ^{[3
]}

Yang, Xiao-Jun ^{[1
,2
]}

Ping, Yi-Fang ^{[1
,2
]}

Duan, Jiang Jie ^{[1
,2
]}

Jiang, Jian-Yong ^{[1
,2
]}

Ye, Xian-Zong ^{[1
,2
]}

Xu, Sen-Lin ^{[1
,2
]}

Xin, Yang-Hong ^{[1
,2
]}

Yao, Xiao-Hong ^{[1
,2
]}

Chen, Jian-Hong ^{[1
,2
]}

Chu, Wei-Hua ^{[4
]}

Sun, Wei ^{[5
]}

Wang, Bing ^{[1
,2
]}

Wang, Ji Ming ^{[6
]}

Zhang, Xia ^{[1
,2
]}

Bian, Xiu-Wu ^{[1
,2
]}

机构：

[1] Third Mil Med Univ, Inst Pathol, Southwest Hosp, Chongqing 400038, Peoples R China

[2] Third Mil Med Univ, SW Canc Ctr, Southwest Hosp, Chongqing 400038, Peoples R China

[3] Third Mil Med Univ, Cent Lab, Southwest Hosp, Chongqing 400038, Peoples R China

[4] Third Mil Med Univ, Dept Neurosurg, Southwest Hosp, Chongqing 400038, Peoples R China

[5] Third Mil Med Univ, Cent Lab, Chongqing 400038, Peoples R China

[6] NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21701 USA

来源：

STEM CELLS | 2012年 / 30卷 / 02期

基金：

中国国家自然科学基金;

关键词：

Connexin; 43; Glioma stem cells; E-Cadherin; Gap junctional intercellular communication; Invasiveness; Tumorigenicity; JUNCTIONAL INTERCELLULAR COMMUNICATION; HUMAN GLIOBLASTOMA CELLS; BREAST-CANCER CELLS; BETA-CATENIN; GAP-JUNCTIONS; EPIGENETIC REGULATION; GENE-EXPRESSION; LUNG-CANCER; GROWTH; CX43;

D O I：

10.1002/stem.1685

中图分类号：

Q813 [细胞工程];

学科分类号：

100113 [医学细胞生物学];

摘要：

Malfunctioned gap junctional intercellular communication (GJIC) has been thought associated with malignant transformation of normal cells. However, the role of GJIC-related proteins such as connexins in sustaining the malignant behavior of cancer stem cells remains unclear. In this study, we obtained tumorspheres formed by glioma stem cells (GSCs) and adherent GSCs and then examined their GJIC. All GSCs showed reduced GJIC, and differentiated glioma cells had more gap junction-like structures than GSCs. GSCs expressed very low level of connexins, Cx43 in particular, which are key components of gap junction. We observed hypermethylation in the promoter of gap junction protein a1, which encodes Cx43 in GSCs. Reconstitution of Cx43 in GSCs inhibited their capacity of self-renewal, invasiveness, and tumorigenicity via influencing E-cadherin and its coding protein, which leads to changes in the expression of Wnt/beta-catenin targeting genes. Our results suggest that GSCs require the low expression of Cx43 for maintaining their malignant phenotype, and upregulation of Cx43 might be a potential strategy for treatment of malignant glioma. STEM CELLS 2012; 30:108-120.

引用

页码：108 / 120

页数：13

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