Tumor‐associated antigens: Tn antigen, sTn antigen, and T antigen

Abstract

Glycosylation is one of the major posttranslational modifications of proteins. N-glycosylation (Asn-linked) and O-glycosylation (Ser/Thr-linked) are the two main forms. Abnormal O-glycosylation is frequently observed on the surface of tumor cells, and is associated with an adverse outcome and poor prognosis in patients with cancer. O-glycans (Tn, sTn, and T antigen) can be synthesized in the Golgi apparatus with the aid of several glycosyltransferases (such as T-synthase and ST6GalNAc-I) in a suitable environment. The unique molecular chaperone of T-synthase is Cosmc, which helps T-synthase to fold correctly in the endoplasmic reticulum. Dysregulation of these glycosyltransferases, molecular chaperones, or the environment is involved in the dysregulation of O-glycans. Tn, sTn, and T antigen neo- or over-expression occurs in many types of cancer including gastric, colon, breast, lung, esophageal, prostate, and endometrial cancer. This review discusses the major synthetic pathway of O-glycans and the mechanism by which Tn, sTn, and T antigens promote tumor metastasis.

Tn antigen promotes human colorectal cancer metastasis via H‐Ras mediated epithelial‐mesenchymal transition activation

“…It has been well documented that Tn antigen is one of the most expressed tumour antigen found in many human cancers, such as colon, breast, cervix, stomach and skin . Many studies have established an association of Tn antigen expression with cancer progression and metastasis and poor outcome . However, it is still unclear whether Tn antigen plays a causative role in cancer progression and metastasis.…”

“…In the process of O‐glycosylation, the Tn antigen is normally modified to form elongated and complex O‐glycans by a specific galactosyltransferase (T‐synthase) in the Golgi apparatus of cells and is thereby not detectable in normal tissues . T‐synthase and its unique chaperone Cosmc are indispensable for normal O‐glycosylation . As many studies revealed that dysfunction in Cosmc (mutations, deletion, and hypermethylation) is a prevailing mechanism for Tn antigen expression in various human cancers, we focused our attention on the functional role of Tn antigen by induction of Cosmc deficiency.…”

“…10,11 Of note, the expression and activity of T-synthase require an endoplasmic reticulum (ER)-resident molecular chaperone Cosmc. [12][13][14] Dysfunction in T-synthase or Cosmc leads to the expression of Tn antigen, which is indeed a characteristic of abnormal Oglycosylation. 15,16 It has been reported that Tn antigen is detected in almost 90% of human colon cancer whereas it is rarely detected in normal tissue.…”

Cosmc overexpression enhances malignancies in human colon cancer

“…To address this issue, we examined the expression of Tn antigen, T‐synthase, and ppGalNac‐Ts, which are essential components during the process of O‐glycosylation, in CRC cells. Alterations in Tn antigen, T‐synthase and/or ppGalNac‐Ts are indicative of aberrant O‐glycosylation . We first detected Tn antigen expression in both Cosmc‐overexpressing cells via flow cytometry.…”

“…We thereby sought to explore the mechanisms for elevated sion and T antigen production, which was the mechanism for the altered cellular phenotypes. 15 Here we checked the changes of Tn, T-synthase, and several essential ppGalNAc-Ts, which are key components of normal O-glycosylation, 21,24,26…”