β3GnT8 regulates the metastatic potential of colorectal carcinoma cells by altering the glycosylation of CD147.

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 (beta 3GnT8) is a key enzyme that catalyzes the formation of poly-N-acetyllactosamine (polylactosamine) chains on beta 1,6-branched N-glycans in vitro, which is also involved in tumor invasion. In the present study, we analyzed the expression of beta 3GnT8 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 beta 3GnT8 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 beta 3GnT8 expression and HG-CD147 was noted in the colorectal cancer cell lines. To further investigate their relationships, exogenous beta 3GnT8 was introduced into the LS-174T cells, while expression of beta 3GnT8 was downregulated in the LoVo cells. The overexpression of beta 3GnT8 in LS-174T cells increased the level of HG-CD147. Conversely, downregulation of beta 3GnT8 expression in LoVo cells significantly decreased the expression of HG-CD147. HG-CD147 is a major carrier of beta 1,6-branched polylactosamine sugars; therefore, the regulation of beta 3GnT8 significantly altered the beta 1,6-branched polylactosamine structures on CD147. Hence, we suggest that beta 3GnT8 plays a key role in the metastasis of colorectal cancer cells by altering the beta 1,6-branched polylactosamine sugars of CD147.