Faulty protein glycosylation – a process of protein modification– is a hallmark of several cancer forms. But knowledge of how the complex molecular processes might contribute to cancer is sparse. In an effort to change this situation, researchers produced an extensive map of mutations affecting glycosyltransferases – offering insight into the mechanisms driving disease.
Post-translational protein modifications are biochemical alterations applied to proteins once cellular protein-making machinery has done its part. There are numerous variants in these alterations, often providing proteins with the final touch necessary for their function. One of the enzyme groups responsible for adding such modifications is glycosyltransferases – adding sugar groups to proteins.
Researchers at Case Western Reserve University School of Medicine took on an ambitious approach, sequencing 430 glycosylation-related genes in cultured cells derived from 31 patients with colon cancer, identifying 12 new genes affected by mutations.
Of these, they found three genes (B3GNT2, B4GALT2, ST6GALNAC2) with a significant amount of mutations. To confirm that the changes were not only found in cultured cells, the team also screened tumor tissue, confirming glycosyltransferase genes were often affected in colon cancer.
Their study, ”Biochemical and functional characterization of glycosylation-associated mutational landscapes in colon cancer,”published in Scientific Reports, could also pinpoint the functional consequences of the mutations, noting that several of them had a direct impact on how proteins behaved in the body, explaining the abnormal protein glycosylation often observed in cancer patients.
“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,” said Kishore Guda, assistant professor of general medical sciences at the School of Medicine, who led the research, in a press release.
“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,” Guda said.