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Cancer Stem Cells
Article first published online: 18 JAN 2012
Copyright © 2011 AlphaMed Press
Volume 30, Issue 2, pages 108–120, February 2012
How to Cite
Yu, S.-C., Xiao, H.-L., Jiang, X.-F., Wang, Q.-L., Li, Y., Yang, X.-J., Ping, Y.-F., Duan, J. J., Jiang, J.-Y., Ye, X.-Z., Xu, S.-L., Xin, Y.-H., Yao, X.-H., Chen, J.-H., Chu, W.-H., Sun, W., Wang, B., Wang, J. M., Zhang, X. and Bian, X.-W. (2012), Connexin 43 Reverses Malignant Phenotypes of Glioma Stem Cells by Modulating E-Cadherin. STEM CELLS, 30: 108–120. doi: 10.1002/stem.1685
Author contributions: S.-C.Y.: conception and design, performance of experiments, data analysis and interpretation, and manuscript writing; H.L.X., X.F.J., J.H.C., W.H.C., Q.L.W., and Y.H.X.: provision of study material or patients; Y.F.P., B.W., and X.Z.Y.: data analysis and interpretation and manuscript writing; Y.L., J.J.D., J.Y.J., X.H.Y., S.L.X., X.F.J., and W.H.S.: data analysis and interpretation; J.M.W. and X.Z.: data interpretation and manuscript revision; X.W.B.: conception and design, financial support, administrative support, data analysis and interpretation, manuscript writing, and final approval of manuscript.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS November 30, 2011.
- Issue published online: 18 JAN 2012
- Article first published online: 18 JAN 2012
- Accepted manuscript online: 30 NOV 2011 01:48PM EST
- Manuscript Accepted: 11 NOV 2011
- Manuscript Received: 1 JUN 2011
- National Basic Research Program of China. Grant Numbers: 973 Program, 2010CB529403
- National Natural Science Foundation of China. Grant Numbers: NSFC, 30725035, 30700863
- Connexin 43;
- Glioma stem cells;
- Gap junctional intercellular communication;
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. STEM CELLS 2012; 30:108-120.