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Abstract

Activation of an aberrant glycosylation pathway in cancer cells can lead to expression of the onco-foetal sialyl-Tn (sTn) antigen. STn is a truncated O-glycan containing a sialic acid α-2,6 linked to GalNAc α-O-Ser/Thr and is associated with an adverse outcome and poor prognosis in cancer patients. The biosynthesis of the sTn antigen has been linked to the expression of the sialytransferase ST6GalNAc1, and also to mutations in and loss of heterozygosity of the COSMC gene. sTn neo- or over-expression occurs in many types of epithelial cancer including gastric, colon, breast, lung, oesophageal, prostate and endometrial cancer. sTn is believed to be carried by a variety of glycoproteins and may influence protein function and be involved in tumour development. This review discusses how the role of sTn in cancer development and tumour cell invasiveness might be organ specific and occur through different mechanisms depending on each cancer type or subtype. As the sTn-antigen is expressed early in carcinogenesis targeting sTn in cancer may enable the targeting of tumours from the earliest stage.

5. The Role of sTn in Cancer Progression

Targeting sTn carrier proteins is a potential cancer therapeutic option. It remains open whether sTn might be carried on cancer stem cell marker proteins but as these proteins can be modified with O-glycans this seems a likely possibility []. The expression of sTn is generally reported to be heterogeneous within tumours [,,,,,] and could be regulated in the tumour via the expression of carrier proteins. As sTn can be carried by different glycoproteins in different compartments, its role in cancer progression may be different in different tumour types, and the effect of sTn expression on tumour cell invasiveness might be organ specific. Together these findings suggest that the biological function of sTn in promoting cancer development may occur through different mechanisms depending on each cancer type or subtype. Future studies using animal models expressing sTn in multiple cancer types and cell backgrounds will help further elucidate the role in sTn in cancer cell invasion and metastasis in different cancers.