ABSTRACT Aberrant mucin‐type O‐glycosylation, mediated by the Polypeptide N‐acetylgalactosaminyltransferase (GALNT) family of enzymes, is a defining feature of many cancers and has also been strongly linked to non‐neoplastic conditions, including developmental disorders and metabolic abnormalities. Mucin‐type O‐GalNAc glycosylation, a prevalent and highly specific form of post‐translational modification, is centrally involved in key processes underlying cancer progression, such as cell signaling, invasion, angiogenesis, and metastasis. It is intricately linked to a diverse array of human diseases, with a particular association with cancer. Ongoing research endeavors to elucidate the functional mechanisms by which GALNT enzymes regulate O‐GalNAc glycosylation, thereby enhancing our understanding of their pivotal roles in cancer biology. Although significant advances have been made in understanding their contributions to cancer initiation and progression, a comprehensive characterization of both the GALNT family and O‐GalNAc glycosylation in oncology remains lacking. This review aims to summarize the structure of the GALNT family and its regulatory roles in the initiation and elongation of O‐GalNAc glycans, providing an in‐depth exploration of the functions of GALNT‐mediated O‐GalNAc glycosylation in cancer. Ultimately, these insights will help uncover underlying oncogenic mechanisms and may offer new potential directions for the development of anticancer therapeutics and diagnostic biomarkers.
Liu et al. (Tue,) studied this question.