Glycans as oncosuppressors
A group of researchers from the Burnham Medical Research Institute, led by Professor Minoru Fukuda, demonstrated that one of the types of polysaccharides that make up cell membranes can act as oncosuppressors in breast and prostate cancer.
The considered type of polysaccharides – N-glycans – in normal cells plays an important role in adhesion (attachment to the intercellular matrix), and a decrease in the number of these molecules on the cell surface or their complete absence contributes to the migration of invasive cancer cells and the spread of metastases. Specialized glycans bind to laminin, the main protein of the cytoskeleton, and attach to the α-DG protein (alpha-dystroglycan) located on the surface of the cell membrane. This bond ensures the adhesion of epithelial cells and basement membrane cells and prevents their free migration. An increase in the expression level of the enzyme involved in the synthesis of such glycans – β1,3-N-acetylglucosaminyltransferase (β3GnT1) – significantly reduces the activity of tumors.
In the course of the study, the expression of the α-DG protein and associated glycans was studied, both in normal cells and in cancer cells. The results showed that the amount of α-DG does not change in cancer cells, but the amount of glycans in them is reduced. Further experiments showed that prostate cancer and breast cancer cells with artificially increased expression of α-DG-associated glycans form smaller tumors compared to the control, and suppression of the expression of the β3GnT1 gene by RNA interference leads to a decrease in the number of synthesized glycans and increased cell migration.
According to the authors, glycans and enzymes involved in their synthesis can be considered as oncosuppressors, at least for the studied types of cancer, and an artificial increase in the expression level of β3GnT1 may be a new technique in the treatment of these diseases.
Portal "Eternal youth" http://vechnayamolodost.ru based on Newswise: Carbohydrate Acts as Tumor Suppressor08.07.2009