High Expression of the Sda Synthase B4GALNT2 Associates with Good Prognosis and Attenuates Stemness in Colon Cancer

Abstract

Background: The carbohydrate antigen Sda and its biosynthetic enzyme B4GALNT2 are highly expressed in normal colonic mucosa but are down-regulated to a variable degree in colon cancer tissues. Here, we investigated the clinical and biological importance of B4GALNT2 in colon cancer. Methods: Correlations of B4GALNT2 mRNA with clinical data were obtained from The Cancer Genome Atlas (TCGA) database; the phenotypic and transcriptomic changes induced by B4GALNT2 were studied in LS174T cells transfected with B4GALNT2 cDNA. Results: TCGA data indicate that patients with high B4GALNT2 expression in cancer tissues display longer survival than non-expressers. In LS174T cells, expression of B4GALNT2 did not affect the ability to heal a scratch wound or to form colonies in standard growth conditions but markedly reduced the growth in soft agar, the tridimensional (3D) growth as spheroids, and the number of cancer stem cells, indicating a specific effect of B4GALNT2 on the growth in poor adherence and stemness. On the transcriptome, B4GALNT2 induced the down-regulation of the stemness-associated gene SOX2 and modulated gene expression towards an attenuation of the cancer phenotype. Conclusions: The level of B4GALNT2 can be proposed as a marker to identify higher- and lower-risk colorectal cancer patients.

The Sda Synthase B4GALNT2 Reduces Malignancy and Stemness in Colon Cancer Cell Lines Independently of Sialyl Lewis X Inhibition

“…This allowed to evaluate the effect of the two glycosyltransferases in two cell lines with different malignancy but with a very close genetic background. In agreement with our previous results on LS174T cells [ 27 ], we found that in both SW480 and SW620 cells B4GALNT2 attenuated in vitro malignancy and stemness. However, the effect on the single properties was very cell-type specific.…”

“…Owing to the marked cell specificity of the effects of glycosyltransferase overexpression we observed in SW480 and SW620 cells, we sought to compare the effects of B4GALNT2 expression in SW480 and SW620 with those previously observed in the B4GALNT2-transfected cell line LS174T [ 27 ]. Statistical analysis was thus performed in search of a “B4GALNT2 signature”, common to the three cell lines.…”

“…This assay was performed as previously described [ 27 ]. Briefly, ALDEFLUOR (Stem Cell technologies, Vancouver, BC, Canada) was added to 5 × 10 5 aliquots of cells.…”

“…Transcriptomic analysis of LS174T cells has been published in Ref. [ 27 ]. The role of the genes in cancer was deduced from a PubMed search.…”

“…The molecular bases of the reduced B4GALNT2 expression in colon cancer are not completely clear, although the methylation of the B4GALNT2 promoter certainly plays a role [ 25 , 26 ]. Transcriptomic data from The Cancer Genome Atlas (TCGA) database indicate that CRC patients with higher B4GALNT2 expression level in cancer tissues display longer overall survival [ 27 ]. In gastrointestinal cancer cell lines, it has been shown that the forced expression of B4GALNT2 resulted in a replacement of the sLe x antigen with the Sd a antigen [ 23 , 28 ].…”