The Cancer-Associated Antigens Sialyl Lewisa/x and Sda: Two Opposite Faces of Terminal Glycosylation
| Autor: | Fabio Dall'Olio, Michela Pucci, Nadia Malagolini |
|---|---|
| Přispěvatelé: | Dall'olio F., Pucci M., Malagolini N. |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Cancer Research
glycosylation Colorectal cancer colorectal cancer Review Biology Sda antigen antigen Antigen gene expression control Gene expression glycosyltransferases medicine B4GALNT2 Sialyl Lewis antigens Stomach cancer skin and connective tissue diseases RC254-282 transcriptomic analysis Sialyl lewis antigen Cancer Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease Phenotype Oncology DNA methylation Cancer cell Cancer research Glycosyltransferase Sd |
| Zdroj: | Cancers Cancers, Vol 13, Iss 5273, p 5273 (2021) |
| ISSN: | 2072-6694 |
| Popis: | Simple Summary The glycosyltransferase β1,4-N-acetylgalactosaminyltransferae 2 (B4GALNT2), product of the B4GALNT2 gene is responsible for the biosynthesis of the carbohydrate antigen Sda. Both the enzyme and its cognate antigen display a restricted pattern of tissue expression and modulation in colorectal, gastric, and mammary cancers. In colorectal cancer, B4GALNT2 is generally downregulated, but patients displaying higher expression survive longer. The sialyl Lewisa and sialyl Lewisx antigens are associated with malignancy. Their biosynthesis and that of Sda are mutually exclusive. Forced expression of B4GALNT2 in colorectal cancer cell lines modulates the transcriptome towards lower malignancy, reducing stemness. These effects are independent of B4GALNT2-induced sLea/sLex inhibition. Thus, B4GALNT2 is a marker of better prognosis and a cancer-restraining enzyme in colorectal cancer, with a therapeutic potential. Abstract Terminal carbohydrate structures are particularly relevant in oncology because they can serve as cancer markers and alter the phenotype of cancer cells. The Sda antigen and the sialyl Lewisx and sialyl Lewisa (sLex and sLea) antigens are terminal structures whose biosynthesis is mutually exclusive. In this review, we describe the main features of the Sda antigen in cancer and its relationship with sLex/a antigens. Information was obtained from an extensive literature search and from The Cancer Genome Atlas (TCGA) public database. The Sda biosynthetic enzyme B4GALNT2 undergoes downregulation in colorectal (CRC) and stomach cancer, while it is ectopically expressed by a minority of breast cancer (BRCA) patients. High expression of B4GALNT2 is associated with better prognosis and a less malignant gene expression profile in CRC, while the opposite occurs in BRCA. The regulation of B4GALNT2 expression in CRC is multifactorial, involving gene methylation and miRNA expression. Forced expression of B4GALNT2 inhibited sLea/sLex and reduced malignancy and stemness in cells constitutively expressing sLex/a antigens. However, consistent effects were observed upon B4GALNT2 forced expression and in cells not expressing sLex/a antigens. Thus, B4GALNT2 and the Sda antigen exert a tumor-restraining activity in CRC and probably other gastrointestinal cancers, independently of sLex/a antigens. |
| Databáze: | OpenAIRE |
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