Role of Sialyl-Tn Antigen in Cancer Metastasis

Glycosylation is the most prominent posttranslational modification of proteins that regulates various protein functions and characteristics. Protein glycosylation is regulated by the cellular expression profile of enzymes regarding glycan and substrate synthesis and the cellular metabolism reflecting cellular status and microenvironments. In the disease process, the glycan synthesis pathway is altered, and aberrant glycans can be generated. Sialyl-Tn (sTn) antigen is a cancer-associated glycan, which is formed on the O-glycans of various proteins. The expression of the sTn antigen correlates with poor prognosis and cancer metastasis, in which sTn antigen plays a pivotal role in the cancer progression. ST6GalNAc-I is a glycosyltransferase responsible for the synthesis of the sTn antigen, the expression of which is induced under hypoxic conditions. In cancer progression, cancer cells benefit from intratumoral microenvironments by exchanging signals to the microenvironments and stromal cells through sTn antigen and its receptor proteins. The function of the sTn antigen is relevant to immune suppression, epithelial-mesenchymal transition, remodeling of the extracellular matrix, invasion, generation and maintenance of cancer stem cells, and metastasis. In this chapter, we introduce the accumulated evidences of the pathophysiological function and significance of the sTn antigen and discuss its role in cancer metastasis.