<i>N</i>‐Glycosylation affects the adhesive function of E‐Cadherin through modifying the composition of adherens junctions (AJs) in human breast carcinoma cell line MDA‐MB‐435

Zhao, Hongbo; Liang, Yulong; Xu, Zhibin; Wang, Liying; Zhou, Feng; Li, Zengxia; Jin, Jun; Yang, Yong; Fang, Zhengyu; Ya-li, HU; Zhang, Lineng; Su, Jialin; Zha, Xiliang

doi:10.1002/jcb.21608

Cited by 53 publications

(50 citation statements)

References 52 publications

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“…However, little is known about the post-transcriptional modifications of E-cadherin and its role in E-cadherin-mediated tumor progression in gastric cancer cells. A substantial body of evidence has appeared to support the view that the E-cadherin function may mainly be affected by mechanisms through N-glycosylation at the post-translational level in some carcinomas (37)(38)(39). However, our data demonstrated that downregulation of GnT-V affected the transcripts of E-cadherin and vimentin, and further influenced the protein expression of E-cadherin and vimentin.…”

Section: Expression Of Invasion-related Factors In the Bgc823/gnt-v Cmentioning

confidence: 48%

Downregulation of the GnT-V gene inhibits metastasis and invasion of BGC823 gastric cancer cells

et al. 2013

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Abstract. Metastatic and invasive potential is a barrier to the successful treatment of gastric cancer. N-acetylglucosaminyltransferase V (GnT-V), a key enzyme catalyzing the formation of 1,6 N-acetylglucosamine (GlcNAc), has been demonstrated to display a distinct function in different types of tumors. The aim of this study was to investigate the role of GnT-V in the invasive potential of BGC823 human gastric cancer cells in vitro and the possible underlying mechanism. GnT-V was downregulated in BGC823 cells by oligo-siRNA transfection. Cell proliferation and invasiveness were assessed by CCK-8 assay, TUNEL assay, scratch-wound assay as well as Transwell assay. The products of GnT-V, β1-6 branching of asparagine-linked oligosaccharides, were determined by L-PHA lectin blot analysis. The expression of EGFRs, E-cadherin/vimentin and MMP-2/MMP-9 was analyzed both at the mRNA and protein levels. The results showed that downregulation of GnT-V decreased proliferation and the metastatic/invasive potential of BGC823 cells. The expression of EGFRs, E-cadherin/vimentin and MMP-9, molecules related to cancer metastasis and invasion in various tumors, were influenced correspondingly. These findings suggest that downregulation of GnT-V inhibited cell metastasis and invasion of BGC823 cells via EGFR signaling-initiated EMT phenotype and MMP-9 expression. These results provide a novel mechanism to explain the role of GnT-V in cell metastasis and invasion.

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Section: Expression Of Invasion-related Factors In the Bgc823/gnt-v Cmentioning

confidence: 48%

Downregulation of the GnT-V gene inhibits metastasis and invasion of BGC823 gastric cancer cells

et al. 2013

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“…Although there might be different interpretations of the structural basis of these experimental observations, the results presented here are consistent with a process in which adhesion triggers subsequent changes in cadherin organization at cell-cell junctions that further enhances binding and is modulated by N-glycans. This study focused on N-cadherin glycosylation, but E-cadherin hyper-glycosylation has been implicated in cadherin dysfunction in cancer (de Freitas Junior et al, 2011;Geng et al, 2004;Pinho et al, 2009a;Pinho et al, 2011;Zhao et al, 2008a). Although phenotypic changes of E-cadherin hypo-glycosylation (Jamal et al, 2009;Nita-Lazar et al, 2010) are qualitatively similar to those reported for N-cadherin (Guo et al, 2009), the glycosylation sites with the greatest impact on E-cadherin-based cell functions appear to be on membrane proximal domains EC4-EC5 (Liwosz et al, 2006).…”

Section: Discussionmentioning

confidence: 89%

“…A large number of studies link aberrant glycosylation to altered cadherin-dependent cell functions, in the context of different cancers. Phenotypic changes include altered cell motility in scratch-wound healing assays, cytoskeleton reorganization, metastasis, ERK signaling and barrier function (Bajpai et al, 2008;Guo et al, 2009;Jamal et al, 2009;Liwosz et al, 2006;Pinho et al, 2009a;Pinho et al, 2011;Vagin et al, 2008;Zhao et al, 2008a). In the case of N-cadherin, the N-glycosylation sites at N273, N325 and N402 are highly conserved.…”

Section: Discussionmentioning

confidence: 99%

N-Glycosylation Alters Cadherin-Mediated Intercellular Binding Kinetics

Langer

Guo

Shashikanth

et al. 2012

Journal of Cell Science

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SummaryWe present direct evidence that the N-glycosylation state of neural cadherin impacts the intrinsic kinetics of cadherin-mediated intercellular binding. Micropipette manipulation measurements quantified the effect of N-glycosylation mutations on intercellular binding dynamics. The wild-type protein exhibits a two-stage binding process in which a fast, initial binding step is followed by a short lag and second, slower transition to the final binding stage. Mutations that ablate N-glycosylation at three sites on the extracellular domains 2 and 3 of neural cadherin alter this kinetic fingerprint. Glycosylation does not affect the affinities between the adhesive Nterminal domains, but instead modulates additional cadherin interactions, which govern the dynamics of intercellular binding. These results, together with previous findings that these hypo-glycosylation mutations increase the prevalence of cis dimers on cell membranes, suggest a binding mechanism in which initial adhesion is followed by additional cadherin interactions, which enhance binding but are modulated by N-glycosylation. Given that oncogene expression drives specific changes in N-glycosylation, these results provide insight into possible mechanisms altering cadherin function during tumor progression.

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“…Junctional stability is associated with a switch in cadherin conformation (44,45), and it is possible that recruitment to the galectin lattice may impede clustering and alter N-cadherin conformation and recruitment of intracellular partners. Indeed, it was shown that E-cadherin hyperglycosylation results in immature and less stable cell adhesions due to increased spacing between dimers and differential recruitment of intracellular partners at cell-cell contacts (46,47).…”

Section: Discussionmentioning

confidence: 99%

Galectin-3 Protein Regulates Mobility of N-cadherin and GM1 Ganglioside at Cell-Cell Junctions of Mammary Carcinoma Cells

Boscher

Zheng

Lakshminarayan

et al. 2012

Journal of Biological Chemistry

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Background: Galectin-3-N-glycan binding forms a lattice that regulates cancer cell adhesion, migration, and signaling. Results: Galectin-3 destabilizes cell-cell junctions and increases junctional mobility of N-cadherin and GM1 ganglioside. Conclusion: Galectin-3 is a novel regulator of N-cadherin dynamics and cell-cell junction stability. Significance: First demonstration of galectin-3 regulation of both glycoprotein and glycolipid mobility defines novel roles for the galectin lattice in junctional stability.

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N‐Glycosylation affects the adhesive function of E‐Cadherin through modifying the composition of adherens junctions (AJs) in human breast carcinoma cell line MDA‐MB‐435

Cited by 53 publications

References 52 publications

Downregulation of the GnT-V gene inhibits metastasis and invasion of BGC823 gastric cancer cells

Downregulation of the GnT-V gene inhibits metastasis and invasion of BGC823 gastric cancer cells

N-Glycosylation Alters Cadherin-Mediated Intercellular Binding Kinetics

Galectin-3 Protein Regulates Mobility of N-cadherin and GM1 Ganglioside at Cell-Cell Junctions of Mammary Carcinoma Cells

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