Role of Truncated O -GalNAc Glycans in Cancer Progression and Metastasis in Endocrine Cancers.

Simple Summary: The surface of a human cell is coated by glycans, which play an important role in many of the physiological processes that include cell–cell communication, interaction, and adhesion. The aberration of the process of glycan synthesis plays a role in inflammatory conditions, tumour progression and metastasis. The process of O-glycosylation is complex and takes place in the Golgi apparatus, regulated by specific enzymes called ppGalNAc transferases. The incomplete synthesis or truncated forms of O-glycans such as Tn, STn, T and ST antigens are commonly seen in cancer states. The increased expression of these truncated glycans is associated with increased invasion potential, leading to metastasis and poor prognosis in a wide range of cancers. Understanding the expression of truncated glycans by cancers paves the way for targeted therapies, which have the potential to be used as serum biomarkers of disease progression and prognosis. Glycans are an essential part of cells, playing a fundamental role in many pathophysiological processes such as cell differentiation, adhesion, motility, signal transduction, host–pathogen interactions, tumour cell invasion, and metastasis development. These glycans are also able to exert control over the changes in tumour immunogenicity, interfering with tumour-editing events and leading to immune-resistant cancer cells. The incomplete synthesis of O-glycans or the formation of truncated glycans such as the Tn-antigen (Thomsen nouveau; GalNAcα- Ser/Thr), its sialylated version the STn-antigen (sialyl-Tn; Neu5Acα2–6GalNAcα-Ser/Thr) and the elongated T-antigen (Thomsen–Friedenreich; Galβ1-3GalNAcα-Ser/Thr) has been shown to be associated with tumour progression and metastatic state in many human cancers. Prognosis in various human cancers is significantly poor when they dedifferentiate or metastasise. Recent studies in glycobiology have shown truncated O-glycans to be a hallmark of cancer cells, and when expressed, increase the oncogenicity by promoting dedifferentiation, risk of metastasis by impaired adhesion (mediated by selectins and integrins), and resistance to immunological killing by NK cells. Insight into these truncated glycans provides a complimentary and attractive route for cancer antigen discovery. The recent emergence of immunotherapies against cancers is predicted to harness the potential of using such agents against cancer-associated truncated glycans. In this review, we explore the role of truncated O-glycans in cancer progression and metastasis along with some recent studies on the role of O-glycans in endocrine cancers affecting the thyroid and adrenal gland. [ABSTRACT FROM AUTHOR]