title: Connexin 43 reverses malignant phenotypes of glioma stem cells by modulating E-cadherin.
abstract: 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 α1, 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/β-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.
authors: Institute of Pathology and Southwest Cancer Center, Third Military Medical University, Chongqing, China.
authors: Shi-Cang
authors: SC
authors: Yu
authors: Hua-Liang
authors: HL
authors: Xiao
authors: Xue-Feng
authors: XF
authors: Jiang
authors: Qing-Liang
authors: QL
authors: Wang
authors: Yan
authors: Y
authors: Li
authors: Xiao-Jun
authors: XJ
authors: Yang
authors: Yi-Fang
authors: YF
authors: Ping
authors: Jiang Jie
authors: JJ
authors: Duan
authors: Jian-Yong
authors: JY
authors: Jiang
authors: Xian-Zong
authors: XZ
authors: Ye
authors: Sen-Lin
authors: SL
authors: Xu
authors: Yang-Hong
authors: YH
authors: Xin
authors: Xiao-Hong
authors: XH
authors: Yao
authors: Jian-Hong
authors: JH
authors: Chen
authors: Wei-Hua
authors: WH
authors: Chu
authors: Wei
authors: W
authors: Sun
authors: Bing
authors: B
authors: Wang
authors: Ji Ming
authors: JM
authors: Wang
authors: Xia
authors: X
authors: Zhang
authors: Xiu-Wu
authors: XW
authors: Bian
mesh_terms: D000328:Adult; D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002450:Cell Communication; D049109:Cell Proliferation; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D005260:Female; D017629:Gap Junctions / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000473:pathology*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D010641:Phenotype; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D018874:Spheroids, Cellular / Q000378:metabolism / Q000648:ultrastructure; D014407:Tumor Cells, Cultured; D060449:Wnt Signaling Pathway
chemical_list: D015820:Cadherins; D018031:Connexin 43; C500216:GJA1 protein, human