PMID:14561752

Citation	Guo, HB, Lee, I, Kamar, M and Pierce, M (2003) N-acetylglucosaminyltransferase V expression levels regulate cadherin-associated homotypic cell-cell adhesion and intracellular signaling pathways. J. Biol. Chem. 278:52412-24
Abstract	A common glycan alteration in transformed cells and human tumors is the highly elevated levels of N-linked beta(1,6)glycans caused by increased transcription of N-acetylglucosaminyltransferase V (GnT-V). Here, we define the involvement of GnT-V in modulation of homotypic cell-cell adhesion in human fibrosarcoma HT1080 and mouse NIH3T3 cells. Increased GnT-V expression resulted in a significant decrease in the rates of calcium-dependent cell-cell adhesion. Reduced cell-cell adhesion was blocked by function-blocking antibody against N-cadherin and abrogated by pre-treatment of cells with swainsonine, demonstrating the involvement of N-cadherin in the cell-cell adhesion and that changes in N-linked beta(1,6)glycan expression are responsible for the reduction in rates of adhesion, although this reduction could be mediated by the altered N-linked glycosylation of glycoproteins other than N-cadherin. Overexpression of GnT-V had no effect on the levels of cell surface expression of N-cadherin; however, it did cause a marked enhancement of both beta(1,6) branching and poly-N-acetyllactosamine expression on N-cadherin. GnT-V overexpression resulted in decreased N-cadherin clustering on the cell surface induced by anti-N-cadherin antibody and affected the outside-in signal transduction pathway of ERK mediated by N-cadherin. Overexpression of GnT-V sensitized stimulation of tyrosine phosphorylation of catenins by growth factors and expression of v-src, which is consistent with its reduction of cell-cell adhesion. In vitro, GnT-V-overexpressing cells showed increased motility concomitant with increased phosphorylation of catenins. Moreover, GnT-V-deficient embryo fibroblasts from GnT-V homozygous null mice (GnT-V(-/-)) express N-cadherin and showed significantly increased levels of N-cadherin-based cell-cell adhesion compared with those from GnT-V(+/-) mice. These levels of adhesion were inhibited significantly by transient expression of GnT-V, confirming the hypothesis that levels of GnT-V can regulate cadherin-associated homotypic cell-cell adhesion. Aberrant N-linked beta(1,6) branching that occurs during oncogenesis can, therefore, lessen cell-cell adhesion, contributing to increased cellular motility and invasiveness.
Links	PubMed Online version:10.1074/jbc.M308837200
Keywords	Animals; Biotinylation; Cadherins/metabolism; Calcium/metabolism; Cell Adhesion; Cell Line; Cell Line, Tumor; Cell Membrane/metabolism; Cell Movement; Electrophoresis, Polyacrylamide Gel; Fibroblasts/metabolism; Flow Cytometry; Growth Substances; Homozygote; Humans; Immunoblotting; Lectins/metabolism; Mice; Mitogen-Activated Protein Kinases/metabolism; N-Acetylglucosaminyltransferases/biosynthesis; NIH 3T3 Cells; Phosphorylation; Precipitin Tests; Signal Transduction; Transfection; Tyrosine/metabolism
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