ST6GalNAc I expression in MDA-MB-231 breast cancer cells greatly modifies their O-glycosylation pattern and enhances their tumourigenicity

Abstract

Sialyl-Tn is a carbohydrate antigen overexpressed in several epithelial cancers, including breast cancer, and usually associated with poor prognosis. Sialyl-Tn is synthesized by a CMP-Neu5Ac:GalNAcalpha2,6-sialyltransferase: CMP-Neu5Ac: R-GalNAcalpha1-O-Ser/Thr alpha2,6-sialyltransferase (EC 2.4.99.3) (ST6GalNAc I), which transfers a sialic acid residue in alpha2,6-linkage to the GalNAcalpha1-O-Ser/Thr structure. However, established breast cancer cell lines express neither ST6GalNAc I nor sialyl-Tn. We have previously shown that stable transfection of MDA-MB-231, a human breast cancer cell line, with ST6GalNAc I cDNA induces sialyl-Tn antigen (STn) expression. We report here the modifications of the O-glycosylation pattern of a MUC1-related recombinant protein secreted by MDA-MB-231 sialyl-Tn positive cells. We also show that sialyl-Tn expression and concomitant changes in the overall O-glycan profiles induce a decrease of adhesion and an increase of migration of MDA-MB-231. Moreover, STn positive clones exhibit an increased tumour growth in severe combined immunodeficiency (SCID) mice. These observations suggest that modification of the O-glycosylation pattern induced by ST6GalNAc I expression are sufficient to enhance the tumourigenicity of MDA-MB-231 breast cancer cells.

Variation in Carbohydrates between Cancer and Normal Cell Membranes Revealed by Super‐Resolution Fluorescence Imaging

“…Thus, previous studies have primarily focused on a limited type of glycosylation events that impart tumor cell properties. Some common alterations of glycosylation have shown to generally accompany with tumorigenesis and metastasis, such as, increase in branches of N‐linked oligoaccharides,7, 8 changed sialylation on certain proteins or antigens,5, 9, 10 abnormal biosynthesis of O‐linked oligosaccharides 11, 12. Owing to the complexity and variability of carbohydrate structures, the cancer‐associated carbohydrate chains have no general changed feature.…”

Loss of Core 1-derived O-Glycans Decreases Breast Cancer Development in Mice

“…Human breast cancer cells show increased expression of sialyltransferase ST6GalNAc1, which can modify Tn to form sialyl Tn (sTn) (26,27). Therefore, deficiency of C1Galt1 may cause compensatory increase of sTn.…”

Glycosylation is a global target for androgen control in prostate cancer cells

“…O-glycan biosynthesis ST6GALNAC1 Sialylation of O-glycans to produce the cancer-associated sTn antigen (Munkley 2016) Associated with poor prognosis in numerous cancer types (Munkley 2016). Promotes tumourigenicity and metastasis in breast and gastric cancer cells (Julien et al 2006, Ozaki et al 2012 ST6GALNAC1 shown to synthesise sTn and reduce cell adhesion in prostate cancer cells (Munkley et al 2015c, Munkley & Elliott 2016b. sTn antigen expressed in high grade prostate tumours (Myers et al 1994, Genega et al 2000.…”