The cytokine-cosmc signaling axis upregulates the tumor-associated carbohydrate antigen Tn

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The cytokine-cosmc signaling axis upregulates the tumor-associated carbohydrate antigen Tn

Tn antigen (GalNAc-α-O-Ser/Thr), a mucin-type O-linked glycan, is a well-established cell surface marker for tumors and its elevated levels have been correlated with cancer progression and prognosis. There are also reports that Tn is elevated in inflammatory tissues. However, the molecular mechanism for its elevated levels in cancer and inflammation is unclear. In the current studies, we have e...

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Expression of tumor-associated carbohydrate antigen Tn in cancer cells is stimulated by cytokine secreted from cancer cells

Tumour-associated carbohydrate antigen (TACA) Tn is always observed on the cell surface of malignant tumour cells. Tn is presented as mucin-type carbohydrate. It has been reported to be associated with cancer progression, but the regulation on Tn expression in cancer cells is not fully understood. In this study, we took an effort to explore the mechanism of how Tn expression is regulated in can...

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Human tumor antigens Tn and sialyl Tn arise from mutations in Cosmc.

Neoplastic lesions typically express specific carbohydrate antigens on glycolipids, mucins, and other glycoproteins. Such antigens are often under epigenetic control and are subject to reversion and loss upon therapeutic selective pressure. We report here that two of the most common tumor-associated carbohydrate antigens, Tn and sialyl Tn (STn), result from somatic mutations in the gene Cosmc t...

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Epigenetic silencing of the chaperone Cosmc in human leukocytes expressing tn antigen.

Cosmc is the specific molecular chaperone in the endoplasmic reticulum for T-synthase, a Golgi β3-galactosyltransferase that generates the core 1 O-glycan, Galβ1-3GalNAcα-Ser/Thr, in glycoproteins. Dysfunctional Cosmc results in the formation of inactive T-synthase and consequent expression of the Tn antigen (GalNAcα1-Ser/Thr), which is associated with several human diseases. However, the molec...

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Aberrant Cosmc genes result in Tn antigen expression in human colorectal carcinoma cell line HT-29.

The Tn antigen, which arises from mutation in the Cosmc gene is one of the most common tumor associated carbohydrate antigens. Cosmc resides in X24 encoded by a single gene and functions as a specific molecular chaperone for T-synthase. While the Tn antigen cannot be detected in normal cells, Cosmc mutations inactivate T-synthase and consequently result in Tn antigen expression within certain c...

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ژورنال

عنوان ژورنال: Oncotarget

سال: 2016

ISSN: 1949-2553

DOI: 10.18632/oncotarget.11324