Abstract
Numerous studies have shown that changes in the glycan structures of cells correlate with tumorigenesis, however, a casual link between the altered glycan structures and the abnormal GJIC in cancer cells is rarely studied. In this paper, we investigated the effects of sialic acid on the Cx43 gap junction functions, and clarified its potential mechanisms thereby. Sialidase significantly increased Cx43 gap junction functions in constructed Cx43-Hela cells along with down-regulation of cell surface sialic acid, which is dramatically reversed by sialidase inhibitor NeuAc2en. Further study indicated that sialidase failed to affect Cx43 at either protein or phosphorylation level, instead, it induced a considerable fraction of Triton X-100 insoluble, as compared with the untreated cells. We also found that sialidase treatment reduced the N-cadherin glycosylation and enhanced both Cx43–ZO-1 interaction and N-cadherin–ZO-1 association. Moreover, sialidase promoted the cell–cell adhesion with elevating N-cadherin binding to β-catenin, accompanied by increasing colocalization of Cx43 with microtubules at the cell periphery. Based on live cell microscopy, with the FARP technology in the Cx43-EGFP-Hela cells, we found that Cx43 in the plague recovered more quickly in sialidase treatment group, indicating that sialidase could promote the Cx43 traffic to the plague. Overall, these studies indicate cell surface sialic acid on cancer cells may suppress Cx43 gap junction functions via inhibiting Cx43 traffic to the plague involving in sialylated N-cadherin, a process that likely underlies the intimate association between abnormal GJIC and glycosylation on cancer development.
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Acknowledgments
We thank Dr. Ben Giepmans for pEGFP-N1-hCx43 plasmid. This work was supported by National Basic Research Program Grant (2003CB716400) of China and Important Science & Technology Specific Projects of Shandong Province (2007GG2TC02048).
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Li, J., Cheng, L., Wang, Lj. et al. Cell surface sialic acid inhibits Cx43 gap junction functions in constructed Hela cancer cells involving in sialylated N-cadherin. Mol Cell Biochem 344, 241–251 (2010). https://doi.org/10.1007/s11010-010-0548-9
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DOI: https://doi.org/10.1007/s11010-010-0548-9