The impact of ST6Gal-I in the progression of colorectal cancer

One of the hallmarks associated with cancer is an aberrant expression of glycans decorating the plasma membrane due to altered expression of glycosyltransferases. The elevation of sialyltransferase ST6Gal-I and of its cognate glycan structure Sia6LacNAc has been described in colon and other cancers and controversially associated with malignancy. In this study, we investigated the relationship between ST6Gal-I mRNA expression and clinical features in a cohort of over 600 colorectal cancer (CRC) cases on The Cancer Genome Atlas, finding that low ST6Gal-I expression was associated with a microsatellite unstable and mucinous phenotype, and with BRAF mutation, but not with clinical stage or survival. To investigate the effect of ST6Gal-I overexpression on CRC, we retrovirally transduced with the human ST6Gal-I cDNA or with an empty vector the cell lines SW48 (microsatellite unstable) and SW948 (chromosomal unstable), generating their ST and NC variants respectively. Transcriptomic analysis of the two cell lines revealed a higher number of modulated genes in SW948 ST compared with SW48 ST. SW948 ST (but not SW48 ST) displayed an accelerated apoptotic response compared to NC, while SW948 ST (but not SW48 ST) displayed increased ability to heal the wound than SW948 NC. In soft agar assay, SW948 ST (but not SW48 ST) cells generated fewer clones, although bigger, than SW948 NC. SW48 ST (but not SW948 ST) displayed a reduced capacity to invade Matrigel compared to NC. Treatment with HGF caused an increase of FAK phosphorylation in SW948 NC cells and a decrease in ST cells. Similar results were observed in SW48 NC and ST cells. With ALDH staining we observed a population of cancer stem cells in the two cell lines with no differences derived from ST6Gal-I overexpression. These results indicate a very cell type specific effect of ST6GAL1 and Sia6LacNAc on the phenotype of CRC cells.