Sialic Acid Glycosylation Alterations

David Nowack (Chemistry)

Sialic acid glycosylation alterations associated with pancreatic cancer Epithelial-Mesenchymal Transition (EMT)

The lethal nature of pancreatic cancer is related to its tendency to metastasize at an early stage and its resistance to chemotherapy. Cancer cells of other origins are known to undergo epithelialmesenchymal transition (EMT) which acquire those same traits and EMT may play an important role in pancreatic cancer progression. Among other significant changes, preliminary experiments testing the pancreatic cancer-EMT link have revealed a pattern of elevated reproduction of the gene ST6GALNAC4, whose protein product is an enzyme that transfers sialic acid to unique carbohydrate structures on a wide variety of proteins.

Following the EMT of cultured pancreatic cancer cells, which set of proteins has its sialic acid glycosylyation patterns changed and the functional impact of the changes is unknown. This longterm project is intended to investigate these unknowns. Using microarray antibody and microarray lectin (proteins that bind specific carbohydrates such as sialic acid) technology, we will determine the composition of the altered glycoproteins, if any, following the increased reproduction of that ST6GALNAC4 gene. Also, the functional significance of the sialic acid changes will be explored, although the exact nature of the experiments needed to probe the functional changes has yet to be established.

The funds requested by this proposal will fund travel and related expenses to continue this productive collaboration with Dr. Brian Haab, Ph.D., of the Van Andel Institute of Grand Rapids, Michigan.






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