1. Connexin 43 reverses malignant phenotypes of glioma stem cells by modulating E-cadherin.
- Author
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Yu SC, Xiao HL, Jiang XF, Wang QL, Li Y, Yang XJ, Ping YF, Duan JJ, Jiang JY, Ye XZ, Xu SL, Xin YH, Yao XH, Chen JH, Chu WH, Sun W, Wang B, Wang JM, Zhang X, and Bian XW
- Subjects
- Adult, Animals, Cadherins genetics, Cell Communication, Cell Proliferation, Connexin 43 genetics, DNA Methylation, Female, Gap Junctions metabolism, Gene Expression Regulation, Neoplastic, Humans, Male, Mice, Mice, Nude, Middle Aged, Neoplasm Invasiveness, Neoplasm Transplantation, Phenotype, Promoter Regions, Genetic, Protein Binding, Spheroids, Cellular metabolism, Spheroids, Cellular ultrastructure, Tumor Cells, Cultured, Wnt Signaling Pathway, Cadherins metabolism, Connexin 43 metabolism, Glioma pathology, Neoplastic Stem Cells metabolism
- 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., (Copyright © 2011 AlphaMed Press.)
- Published
- 2012
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