Protein glycosylation represents a nearly ubiquitous post-translational modification, and altered glycosylation can result in clinically significant pathological consequences. Here we focus on O-glycosylation in tumor cells of mice and humans. O-glycans are those linked to serine and threonine (Ser/Thr) residues via N-acetylgalactosamine (GalNAc), which are oligosaccharides that occur widely in glycoproteins, such as those expressed on the surfaces and in secretions of all cell types. The structure and expression of O-glycans are dependent on the cell type and disease state of the cells. There is a great interest in O-glycosylation of tumor cells, as they typically express many altered types of O-glycans compared with untransformed cells. Such altered expression of glycans, quantitatively and/or qualitatively on different glycoproteins, is used as circulating tumor biomarkers, such as CA19-9 and CA-125. Other tumor-associated carbohydrate antigens (TACAs), such as the Tn antigen and sialyl-Tn antigen (STn), are truncated O-glycans commonly expressed by carcinomas on multiple glycoproteins; they contribute to tumor development and serve as potential biomarkers for tumor presence and stage, both in immunohistochemistry and in serum diagnostics. Here we discuss O-glycosylation in murine and human cells with a focus on colorectal, breast, and pancreatic cancers, centering on the structure, function and recognition of O-glycans. There are enormous opportunities to exploit our knowledge of O-glycosylation in tumor cells to develop new diagnostics and therapeutics.
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Cover Image
Cover Image
Glutamine transport across cell membranes is performed by a variety of transporters, including the alanine serine cysteine transporter 2 (ASCT2). The substrate-binding site of ASCT2 was proposed to be specific for small amino acids with neutral side chains, excluding basic substrates such as lysine. In this issue Ndaru and co-workers (pp. 1443–1457) expand the substrate specificity of ASCT2 to include amino acid substrates with positively charged side chains. The image shows the docking pose of L-DAB and L-DAP, from the side view of the ASCT2 homology model in the outward-open conformation.The image was provided by Christof Grewer.
O-glycan recognition and function in mice and human cancers
Gabrielle E. Cervoni, Jane J. Cheng, Kathryn A. Stackhouse, Jamie Heimburg-Molinaro, Richard D. Cummings; O-glycan recognition and function in mice and human cancers. Biochem J 30 April 2020; 477 (8): 1541–1564. doi: https://doi.org/10.1042/BCJ20180103
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