Cervoni Gabrielle E, Cheng Jane J, Stackhouse Kathryn A, Heimburg-Molinaro Jamie, Cummings Richard D
Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, CLS 11087, 3 Blackfan Circle, Boston, MA 02115, U.S.A.
Biochem J. 2020 Apr 30;477(8):1541-1564. doi: 10.1042/BCJ20180103.
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.
蛋白质糖基化是一种几乎普遍存在的翻译后修饰，糖基化改变可导致具有临床意义的病理后果。在此，我们聚焦于小鼠和人类肿瘤细胞中的O-糖基化。O-聚糖是通过N-乙酰半乳糖胺（GalNAc）与丝氨酸和苏氨酸（Ser/Thr）残基相连的聚糖，广泛存在于糖蛋白中，如在所有细胞类型的表面和分泌物中表达的糖蛋白。O-聚糖的结构和表达取决于细胞类型和细胞的疾病状态。肿瘤细胞的O-糖基化备受关注，因为与未转化细胞相比，它们通常表达多种改变类型的O-聚糖。聚糖在不同糖蛋白上的这种定量和/或定性的改变表达，被用作循环肿瘤生物标志物，如CA19-9和CA-125。其他肿瘤相关碳水化合物抗原（TACA），如Tn抗原和唾液酸化Tn抗原（STn），是癌组织在多种糖蛋白上常见表达的截短O-聚糖；它们有助于肿瘤发展，并在免疫组织化学和血清诊断中作为肿瘤存在和分期的潜在生物标志物。在此，我们讨论小鼠和人类细胞中的O-糖基化，重点关注结直肠癌、乳腺癌和胰腺癌，围绕O-聚糖的结构、功能和识别展开。利用我们对肿瘤细胞O-糖基化的了解来开发新的诊断方法和治疗手段，存在巨大的机会。
