Study of the B3GNT7 and IGnTA glycosyltransferase genes: Functional role in colon cancer metastasis and their regulatory mechanisms
Date Issued
2012
Date
2012
Author(s)
Lu, Chun-Hao
Abstract
The glycans on the surfaces of gastrointestinal tract-related cancer cells undergo remarkable changes during malignant transformation. The glycans specially expressing on the surfaces of cancer cells are called tumor-associated glycans. Sialyl Lewis a (sLea) and sialyl Lewis x (sLex) are the most famous tumor-associated glycans in gastrointestinal cancers. Previous studies indicated that sLea and sLex expression would promote the metastasis of gastrointestinal cancers and correlate with the risk of recurrence and the survival rate of a patient. sLea and sLex are constructed on the terminals of poly-LacNAc chains composed of repeated N-acetyllactosamine (Gal-GlcNAc，LacNAc) unit. In our previous research, we found that the expression of two glyco-genes, β-1,3-N-acetylglucosaminyltransferase 7 (B3GNT7) and I-branching β-1,6-N-acetylglucosaminyltransferase (IGnTA), which are involved in the biosynthesis of poly-LacNAc chains, are down-regulated in the tumor tissues of the patients with colon cancer. Therefore, the issues what we want to discuss are whether colon cancer cells would alter sLea and sLex expression and thereby affect colon cancer metastasis when the synthesis of poly-LacNAc chains on cell surfaces is altered.
We used colon cancer cell lines as the cell models in our research to examine the effects of B3GNT7 and IGnTA expression on colon cancer metastasis and the mechanisms resulting in down-regulation of B3GNT7 and IGnTA in colon cancer cells. We found that sLea and sLex expression and the extent of colon cancer metastasis in colon cancer cells with over-expressing of B3GNT7 and IGnTA respectively are less than those of control cells. We also found that there are highly-methylated CpG islands in B3GNT7 and the 5’-regulated region of IGnTA in colon cancer cells. After treating colon cancer cells with the demethylating reagent, 5-Aza-2’-deoxycytidine (5AzadC), we found B3GNT7 and IGnTA expression are elevated and the extent of CpG islands methylation in B3GNT7 and the 5’-regulated region of IGnTA decreased. Therefore, the mechanisms regulating B3GNT7 and IGnTA expression in colon cancer cells are highly correlated with DNA methylation. Furthermore, we found that IGnTA expression increase and sLea expression decreases in colon cancer cells with treatments of epigenetic drugs, including 5AzadC and histone deacetylase inhibitors (HDAC inhibitors).
In this research, we demonstrated that in colon cancer cells, B3GNT7 and IGnTA may play important roles in colon cancer metastasis and their expression pattern would affect sLea and sLex expression and DNA methylation may participate in the regulations of B3GNT7 and IGnTA expression.
Subjects
tumor-associated antigen
metastasis
colon cancer cell line
methylation
histone acetylase inhibitor
SDGs
Type
thesis
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