Enzyme Defines Colon Cancer

A new enzyme has been identified by researchers that are absent in healthy colon tissue but abundant in colon cancer cells. The Journal of Biological Chemistry has published the report. It appears that the enzymes drive the conversion of normal colon tissue into cancer by attaching sugar molecules, or glycans, to specific proteins in the cell. Sugar-modified (glycosylated) proteins play a role in healthy and cancerous cells and is an emerging area of cancer biology that may lead to new therapies.

A team at the University of Copenhagen that was led by Hans Wandall studied a group of 20 lenses that initiate the first step in a particular kind of glycan modification, called GalNAc-type O-glycosylation, that are found on diverse proteins. These enzymes are variously found in different amounts in different tissues, but the functions are poorly understood.

The team was led by a graduate student by the name of Kristine Larsen, who found one of the GalNAc-Ts, called GalNAc-T6, was absent in healthy colon tissue but abundant in colon cancer cells. They used CRISPR/Was engineering of a colon cancer cell line with and without GalNAc-T6 to understand which proteins the enzyme helped attached sugars to as well as what effect this had on the cells.

When they take out GalNAc-T6, the tissue suddenly changes formation to look more like the crypt structures that are found in a healthy colon. The team categorized the proteins that GalNAc-T6 acted on in these cells. This specific enzyme seems to affect a subset of proteins that could be involved in cell-cell adhesion. The modifications changed the cells to develop as something that looked like a tumor more than healthy tissue.

Glycan modifications can affect protein function in may ways. They hope that understanding glycosylation in cancer cells will lead to a better early diagnostic tool, drugs or immunotherapies. Glycans look different in cancer compared to normal tissue and is an understudied field.

They need to further explore disruptions in a protein-processing pathway that appear to promote aggressive proliferation and invasion in tumor cells.

Dr Fredda Branyon