Synthesis of Sialyl-Tn Antigen (STn) Type O-Glycan and Its Relevance to Cancer

STn is a product of an incomplete glycosylation process and is the Sialylated form of Tn antigen. Its synthesis is found to be associated with salivary acid transferase ST6GalNAc1 and the mutations, deletions, and heterozygosity in the Cosmic genes. GalNAc on UDP-GalNAc is attached to a serine-threonine residue. Sialic acid is transferred to GalNAc for the synthesis of sTn catalyzed by ST6GalNAc1. STn synthesis is found to be heterogeneous. Glycoproteins carrying sTn differ in different cells. In vitro, sTn can be synthesized by mediating the specific sialic acid transferase ST6GalNAc1 and ST6Gal NAc2. In the intracellular milieu, only ST6GalNAc1 is able to synthesize sTn. STn is closely associated with carcinogenesis and plays a role in cell adhesion, recognition, etc. sTn is also known as a tumor-associated antigen. Activation of aberrant glycosylation pathways in cancer cells can lead to the expression of sTn. This O-glycan is found in most tumor-associated mucins.

Fig.1 Synthesis of sTn in cancer cells. (Munkley, 2016)

Sialyl-Tn Antigen Type O-glycan Glycoengineering Service at CD BioGlyco

CD BioGlyco has a wealth of knowledge and an innovative team in cancer-related Glycoengineering. STn is a truncated O-glycan. This truncation is associated with some factors. These include alterations in glycosyltransferases, mislocalization of galactosaminyltransferase from the endoplasmic reticulum to the Golgi apparatus, methylation or mutation of Cosmic, etc. More than 80% of cancer cells have expression of sTn antigen. Research on cancer therapeutics targeting sTn is also a hot topic. In order to facilitate our clients in cancer therapeutic research, we have developed a related sTn glycoengineering service.

The expression of sTn in tumors is heterogeneous and may function differently in different tumor cells. We affect sTn synthesis by Regulating the Expression of Enzyme Genes related to sTn synthesis, such as salivary acid transferase ST6GalNAc1 and Cosmic gene. Changes in sTn expression are found to affect the biological characteristics of cancer cells. Some cancer cell lines do not express sTn and ST6GalNAc1 genes. We try to synthesize sTn-type O-glycans by transfecting ST6GalNAc1 to be expressed in cancer cells and detect changes in cancer cell growth, adhesion, etc. We also try to introduce salivary acid analogs into sTn synthesis to influence the final structure of sTn. We have abundant mouse and cell line models and are capable of accomplishing various glycoengineering challenges.

Fig.2 Some projects developed based on sTn-type O-glycans. (CD BioGlyco)

Publication

Paper Title: The ST6GalNAc-I sialyltransferase localizes throughout the Golgi and is responsible for the synthesis of the tumor-associated sialyl-Tn O-glycan in human breast cancer

Technology: Knock-in Technology

Journal: Journal of Biological Chemistry

IF: 4.238

Published: 2006

Results: Two hST6GalNAc genes were cloned from K562 cells and transfected into the breast cancer cell line T47D. The results showed that both enzyme genes were expressed in the Golgi apparatus. Among them, sTn expression was present in T47D cells transfected with hST6GalNAc-I. However, sTn O-glycans were not synthesized in T47D cells transfected with hST6GalNAc-II. This study demonstrated that hST6GalNAc-I was involved in and directed the synthesis of sTn O-glycan.

Fig.3 ST6GalNAc-II does not correlate with sTn expression in breast cancer and does not direct the synthesis of STn in transfected cells. (Sewell, et al., 2006)

Applications

• Glycoengineering technologies have an important role in cancer therapy. STn carrier proteins can be used as a target to develop cancer therapeutics.
• High expression of sTn-type O-glycan is associated with certain aggressive diseases. Glycoengineering techniques are utilized to investigate sTn-type O-glycan-based therapeutic modalities for disease treatment. STn-type O-glycan can be used as a target to develop cancer therapies.
• STn-type O-glycan may have a role in the development of certain diseases. Glycoengineering techniques are used to study the mechanisms of disease development.

Advantages

• We have efficient expression vectors with high transient transfection rates and a shortened experimental cycle.
• The sTn-type O-glycans have great potential for application in cancer therapy. Glycoengineering technology helps researchers explore the role of sTn-type O-glycans in cancer therapy.
• We use high-quality gold-standard antibodies and high-standard modification enrichment operations to improve the accuracy of detection. The results of experimental data are stable and reliable.

CD BioGlyco continues to expand its glycan engineering services related to cancer therapy. With rich experience in glycan engineering, we are capable of accomplishing various challenging tasks. In addition to sTn type O-glycan, we also provide Sialyl-T Antigen Type O-glycan and Mucin Type O-glycan Glycoengineering services. Welcome to contact us for a more detailed experimental program.

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