Glycosylation-associated Gene Mutations Discovered as New Targets in Colon Cancer

Glycosylation-associated Gene Mutations Discovered as New Targets in Colon Cancer

Though the molecular principles of dysfunctional protein glycosylation and the way its enzymatic mechanism is known to cause tumors in such cancers as colorectal cancer (CRC) is not completely understood, the recent study “Biochemical and functional characterization of glycosylation-associated mutational patterns in colon cancer,” published in Scientific Reports, has identified mutational patterns of glycosylation-associated genes in colon cancer, and names three glycosyltransferases as relevant mutational targets.

Glycosylation is the addition of carbohydrates (sugar) to a protein molecule. Enzymes that transfer simple sugars from donor molecules to growing sugar chains or proteins are called glycosyltransferases, which link particular sugars from a donor to substrates that act independently. Glycosidic bonds exist in almost every protein functional group, and glycosylation incorporates most of the commonly occurring simple sugars.

In the recent study by reserarchers at Case Western Reserve University School of Medicine, in Ohio, three glycosyltransferases were recognized as relevant mutational targets in CRC. The mutant glycosyltransferases are influential on the enzymatic activity and the migratory potential of cancer cells in the colon. Although the study does not fully uncover the functional mechanisms and biochemical reactions of glycosylation, the finding in CRC of harmful mutations in genes that are needed to maintain intestinal balance, demonstrates that genetic abnormalities in some glycosylation pathways and other structures might play a key role in CRC development.

Lead researcher Kishore Guda initiated targeted re-sequencing of 430 glycosylation-associated genes and matched primary cancer tissues. The team identified glycosyltransferases B3GNT2, ST6GALNAC2, and B4GALT2 as relevant targets in CRC related mutations. Further investigation of independent large-scale cancer tissue supported the recurrent mutations in relation to colon cancer and other gastrointestinal tumors.

“With so many questions surrounding the potential role of aberrant glycosylation in tumor progression, we were excited to conduct this research that builds on our previous findings of mutations in the gene encoding for the enzyme GALNT12 in a subset of colon cancer cases,” Guda said. “Our findings demonstrate that these mutant glycosyltransferases have a significant impact on the encoded enzymatic activity and/or the migratory potential of colon carcinoma cells, and set up future research that can further explore their role in tumor progression.”

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