title: Cell surface sialic acid inhibits Cx43 gap junction functions in constructed Hela cancer cells involving in sialylated N-cadherin.
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.
authors.affiliation: Department of Pharmacology and Glycobiology, School of Medicine and Pharmacy, Ocean University of China, Qingdao, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Cheng
authors.forename: Li-juan
authors.initials: LJ
authors.lastname: Wang
authors.forename: Hong-chun
authors.initials: HC
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Xiao-lu
authors.initials: XL
authors.lastname: Wang
authors.forename: Mei-yu
authors.initials: MY
authors.lastname: Geng
mesh_terms: D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D018031:Connexin 43 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*
chemical_list: D015820:Cadherins; D018031:Connexin 43; D019158:N-Acetylneuraminic Acid
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