374907

B3GNT8

UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 8;B3GNT8;UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 8

BGnT-8|UDP-Gal:betaGal beta 1,3-galactosyltransferase polypeptide 7|beta galactosyltransferase BGALT15|beta-1,3-Gn-T8|beta-1,3-N-acetylglucosaminyltransferase 8|beta1,3-N-acetylglucosaminyltransferase 8

19q13.2

protein-coding

Changes in glycosylation due to specific alterations of glycosyltransferase activity have been shown in various tumor cells, including human glioma cells. beta1,3-Nacetylglucosaminyltransferase-8 (beta3GnT8) catalyzes the formation of polylactosamine on beta1-6 branched N-glycans. Upregulated expression of beta3GnT8 was described in some tumors, but its precise role in regulating glioma invasion and metastasis remains unclear. In this study, we report on an investigation of the expression of beta3GnT8 in human glioma by immunohistochemical analysis. Out of 42 glioma tissues, 37 (88.1%) showed positive beta3GnT8 expression, which was significantly higher than that in normal brain tissues (P<0.001). Additionally, the level of beta3GnT8 increased with increased pathological grade of gliomas. Silencing of beta3GnT8 in U251 glioma cells attenuated the formation of polylactosamine, and decreased cell proliferation, migration and metastatic ability in vitro and in vivo. By contrast, the overexpression of beta3GnT8 in U251 cells exhibited enhanced metastatic potential. A positive correlation between beta3GnT8 and matrix metalloproteinase-2 (MMP-2) expression in U251 cells was also observed. The results demonstrated a critical role of beta3GnT8 in the metastatic potential of glioma cells, indicating that manipulating beta3GnT8 expression may have therapeutic potential for the treatment of malignant glioma.

Aberrant glycosylation of cell surface glycoproteins is commonly associated with the invasion and metastasis of colorectal carcinomas, which can be attributed to the upregulated expression of glycosyltransferases. Therefore, elucidation of glycosyltransferases and their substrates may improve our understanding of their roles in tumor metastasis. beta-1,3-N-acetylglucosaminyltransferase-8 (beta3GnT8) is a key enzyme that catalyzes the formation of poly-N-acetyllactosamine (polylactosamine) chains on beta1,6-branched N-glycans in vitro, which is also involved in tumor invasion. In the present study, we analyzed the expression of beta3GnT8 and its product polylactosamine in four human colorectal carcinoma cell lines (LS-174T, SW620, SW480 and LoVo) with different metastatic potential. We found that the levels of beta3GnT8 and polylactosamine chains were gradually increased in the colorectal cancer cell lines in a trend from low to high metastatic potential. Notably, a significantly positive relationship between beta3GnT8 expression and HG-CD147 was noted in the colorectal cancer cell lines. To further investigate their relationships, exogenous beta3GnT8 was introduced into the LS-174T cells, while expression of beta3GnT8 was downregulated in the LoVo cells. The overexpression of beta3GnT8 in LS-174T cells increased the level of HG-CD147. Conversely, downregulation of beta3GnT8 expression in LoVo cells significantly decreased the expression of HG-CD147. HG-CD147 is a major carrier of beta1,6-branched polylactosamine sugars; therefore, the regulation of beta3GnT8 significantly altered the beta1,6-branched polylactosamine structures on CD147. Hence, we suggest that beta3GnT8 plays a key role in the metastasis of colorectal cancer cells by altering the beta1,6-branched polylactosamine sugars of CD147.