Academic
Publications
Inhibition of N -linked glycosylation by tunicamycin induces E-cadherin-mediated cell–cell adhesion and inhibits cell proliferation in undifferentiated human colon cancer cells

Inhibition of N -linked glycosylation by tunicamycin induces E-cadherin-mediated cell–cell adhesion and inhibits cell proliferation in undifferentiate

Inhibition of N -linked glycosylation by tunicamycin induces E-cadherin-mediated cell–cell adhesion and inhibits cell proliferation in undifferentiated human colon cancer cells  
BibTex | RIS | RefWorks Download
Purpose  Aberrant protein glycosylation and disassembly of E-cadherin-mediated cell–cell adhesion are characteristics of epithelial cancer. However, the relationship between these two events in colorectal cancer remains to be defined. In this study, we analyzed whether N-glycan expression is crucial for the loss of E-cadherin-mediated cell–cell adhesion in human colorectal cancer cells. Methods  Differentiated Caco-2 and undifferentiated HCT-116 colon cancer cells were used as models of stable and unstable adherens junctions (AJs), respectively. Complex-type N-glycans were detected using the lectins E-PHA (Phaseolus vulgaris E.) and L-PHA (Phaseolus vulgaris L.). To study E-cadherin-mediated AJ assembly, we examined the effects of swainsonine, an inhibitor of α-mannosidase II, and tunicamycin, a drug that inhibits the biosynthesis of N-glycans, via western blot, immunofluorescence, differential extraction in Triton X-100, and electron microscopy. Cell proliferation and apoptosis were examined by crystal violet staining and flow cytometry, respectively. Results  We observed positive labeling for E-PHA and L-PHA lectins in both cell lines; however, HCT-116 cells had increased E-cadherin-linked complex-type N-glycans. Interestingly, tunicamycin, but not swainsonine, was able to induce functional E-cadherin-mediated cell–cell adhesion in undifferentiated HCT-116 cells, as shown by the increased association of E-cadherin with the actin cytoskeleton. Moreover, in HCT-116 cells, tunicamycin also induced the formation of tight cell–cell contacts, and it inhibited cell proliferation without triggering apoptosis. Conclusions  Collectively, our results demonstrate for the first time that altered N-glycan expression plays an important role in the loss of AJ stability in undifferentiated colorectal cancer cells and that this loss may be associated with the progression of colorectal cancer.
Journal: Cancer Chemotherapy and Pharmacology - CANCER CHEMOTHER PHARMACOL , vol. 68, no. 1, pp. 227-238, 2011
Cumulative Annual
View Publication
The following links allow you to view full publications. These links are maintained by other sources not affiliated with Microsoft Academic Search.