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

HLA. 2016 Dec;88(6):275-286. doi: 10.1111/tan.12900. Epub 2016 Sep 28.

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.

Keywords: Cosmc; O-glycosylation; T-synthase; Tn antigen; T antigen; sTn antigen; tumor metastasis.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Tumor-Associated, Carbohydrate / genetics*
  • Antigens, Tumor-Associated, Carbohydrate / metabolism
  • Antigens, Viral, Tumor / genetics*
  • Antigens, Viral, Tumor / metabolism
  • Carbohydrate Sequence
  • Endoplasmic Reticulum / metabolism
  • Galactosyltransferases / genetics
  • Galactosyltransferases / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Glycosylation
  • Golgi Apparatus / metabolism
  • Humans
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism
  • Neoplasm Metastasis
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Protein Folding
  • Protein Processing, Post-Translational*
  • Sialyltransferases / genetics
  • Sialyltransferases / metabolism
  • Tumor Cells, Cultured

Substances

  • Antigens, Tumor-Associated, Carbohydrate
  • Antigens, Viral, Tumor
  • C1GALT1C1 protein, human
  • Molecular Chaperones
  • Neoplasm Proteins
  • Tn antigen
  • C1GALT1 protein, human
  • Galactosyltransferases
  • Sialyltransferases
  • CMP-N-acetylneuraminate-alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase