Tn and sialyl-Tn antigens, aberrant O-glycomics as human disease markers.
Tn and sialyl-Tn antigens, aberrant O-glycomics as human disease markers.
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DOI：
10.1002/prca.201300024
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发表时间：
2013-10
期刊：
影响因子：
--
通讯作者：
Cummings RD
中科院分区：
文献类型：
--
作者：
Ju T;Wang Y;Aryal RP;Lehoux SD;Ding X;Kudelka MR;Cutler C;Zeng J;Wang J;Sun X;Heimburg-Molinaro J;Smith DF;Cummings RD
在许多不同的人类疾病中，细胞糖被改变。粘蛋白型o -糖苷发生了一个有趣但鲜为人知的变化，其中截断的o -聚糖Tn （GalNAcα1-Ser/Thr）及其唾液化版本sialyl-Tn (STn) （neu5ac α2,6GalNAcα1-Ser/Thr）的异常表达。Tn和STn都是肿瘤相关的碳水化合物抗原和肿瘤生物标志物，因为它们不正常表达，在肿瘤发生早期出现。此外，它们的表达与不良预后和肿瘤转移密切相关。Tn和STn抗原也在其他人类疾病和失调中表达，如Tn综合征和IgA肾病。Tn和STn抗原表达的主要病理机制是t合酶活性受损，这是由编码Cosmc的x连锁基因改变引起的，Cosmc是t合酶正确折叠形成活性酶所必需的分子伴侣。本文综述了目前对Tn和STn抗原的生物化学和病理作用的认识。
In many different human disorders, the cellular glycome is altered. An interesting but poorly understood alteration occurs in the mucin-type O-glycome, in which there is aberrant expression of the truncated O-glycans Tn (GalNAcα1-Ser/Thr) and its sialylated version sialyl-Tn (STn) (Neu5Acα2,6GalNAcα1-Ser/Thr). Both Tn and STn are tumor-associated carbohydrate antigens and tumor biomarkers, since they are not expressed normally and appear early in tumorigenesis. Moreover, their expression is strongly associated with poor prognosis and tumor metastasis. The Tn and STn antigens are also expressed in other human diseases and disorders, such as Tn syndrome and IgA nephropathy. The major pathological mechanism for expression of the Tn and STn antigens is compromised T-synthase activity, resulting from alteration of the X-linked gene that encodes for Cosmc, a molecular chaperone specifically required for the correct folding of T-synthase to form active enzyme. This review will summarize our current understanding of the Tn and STn antigens in terms of their biochemistry and role in pathology.
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