Suppression of B3GNT7 gene expression in colon adenocarcinoma and its potential effect in the metastasis of colon cancer cells

Abstract

The cell surface sialyl Lewis a (sLe(a)) and sialyl Lewis x (sLe(x)) antigens, which are built on the terminals of glyco-structures called poly-N-acetyllactosamine (LacNAc) chains, have been shown to play a critical role in the metastasis of colon cancer. In the present investigation, expression of the B3GNT7 gene, which encodes a β-1,3-N-acetylglucosaminyltransferase that mainly acts on and extends sulfated poly-LacNAc chains, was found to be markedly suppressed during the oncogenetic processes associated with colon cancer. DNA methylation in the promoter region of the B3GNT7 gene was found to play a significant role in the suppression of the B3GNT7 gene in colon cancer cells. The results obtained from Transwell experiments and the nude mice xenograft model demonstrated that ectopic expression of the B3GNT7 gene in colon cancer cells diminished the migration capability and the liver-metastasis potential, respectively, of colon cancer cells. Flow cytometric analysis showed that expression of cell surface sLe(a) and sLe(x) antigens was decreased in colon cancer cells when the B3GNT7 gene was ectopically expressed. Taken together, the results of the present investigation suggest a link between suppression of B3GNT7 gene expression and elevation of sLe(a)/sLe(x) antigen expressions on the surface of cells and that this consequently promotes the metastasis potential of cancer cells as part of the colon cancer oncogenetic process.

Predictive properties of DNA methylation patterns in primary tumor samples for osteosarcoma relapse status

“…Gamma secretase associated protein (GSAP), 36 part of the gamma secretase regulatory network, has been well-studied in Alzheimer disease, but its importance to tumorigenesis and survival, especially because of its interactions with gamma secretase (currently the target of multiple therapeutic trials in cancer) remains unexplored. Several members of the b-1-3-N-acetylglucosaminyltransferase family have been implicated in cell invasion and migration of multiple tumor types, [37][38][39] suggesting that b-1-3-N-acetylglucosaminyltransferase 9 (B3GNT9) may play a similar function. Finally, the fibronectins, including FNDC3A, mediate cell adhesion with potential consequences for cancer metastasis.…”

B3GNT3 overexpression is associated with unfavourable survival in non-small cell lung cancer

“…For instance, expression of B3GNT2 is greatly decreased in invasive bladder transitional cell carcinomas in comparison with their non-invasive counterparts, indicating that B3GNT2 may be involved in tumour progression 9. Downregulation of B3GNT7 gene expression is related to the elevation of sialyl Lewis A (sLe(A))/sialyl Lewis X (sLe(X)) antigen expression in colon cancer cells and promotes tumour cell metastasis 10. B3GNT8 expression is upregulated and may have a role in malignant transformation in colorectal cancer, glioma, laryngeal carcinoma and gastric cancer 11–14…”

B4GAT1 is the priming enzyme for the LARGE-dependent functional glycosylation of α-dystroglycan

“…Poly-N-acetyllactosamine chains consist of the repeating disaccharide -β3-GlcNAc-β4-Gal-, a structure termed the i-antigen when unbranched (Ujita et al, 2000; Zhou, 2003). Poly-N-acetyllactosamine is a prevalent glycan substructure found in N-glycans and O-glycans on proteins whose abnormal levels have been associated with human diseases including cancer (Ujita et al, 2000; Zhou, 2003; Ho et al, 2013; Lu et al, 2014). The Fukuda group used an expression cloning strategy enriching for plasmids containing cDNA inserts that substantially increased poly-N-acetyllactosamine, as judged by antibody binding, on the surfaces of Namalwa KJM-1 cells (Sasaki et al, 1997).…”