Effect of staurosporine on N-glycosylation and cell adhesion to fibronectin of SW480 human colorectal adenocarcinoma cells.
As N-glycosylation of tumor cell surface proteins affects metastasis of the cells, it was considered that the suppression of metastasis by staurosporine, a protein kinase C inhibitor, is partly caused by changes in N-glycosylation. To examine this possibility, we studied the glycosylation of membrane proteins of SW480 human colorectal adenocarcinoma cells before and after treatment with staurosporine by lectin blot analysis. The results showed that the reactivity of leuko-agglutinating phytohemagglutinin and Datura stramonium agglutinin, both of which bind to highly branched N-linked oligosaccharides characteristic of cancer cells, decreases significantly in the staurosporine-treated cells. In accordance with this, the gene expression of the N-acetylglucosaminyltransferase V, which synthesizes the GlcNAcbeta1-->6 branch of highly branched N-linked oligosaccharides decreased by 30-40% in the drug-treated cells. Since a decrease in the lectin binding was found in several glycoproteins including fibronectin (FN)-receptor, effect of the changes in N-glycosylation of the cells on cell adhesion to FN-matrix was examined. The results showed that the number of cells attached to FN-matrix increases upon treatment of the cells with staurosporine, indicating that the change of N-glycosylation of the FN-receptor promotes cell adhesion to the extracellular matrix, which may lead to the suppression of metastasis of cancer cells.
Sato
Takeshi
T
Department of Biosignal Research, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo 173-0015, Japan.
Takahashi
Mikiko
M
Kawado
Takeshi
T
Takayama
Eiji
E
Furukawa
Kiyoshi
K
D000230:Adenocarcinoma / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D005353:Fibronectins / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D006031:Glycosylation; D006801:Humans; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism; D009362:Neoplasm Metastasis; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019311:Staurosporine / Q000494:pharmacology*
D005353:Fibronectins; D017351:N-Acetylglucosaminyltransferases; C052254:alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase; D011493:Protein Kinase C; D019311:Staurosporine