A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion

2019 
Proteins, the workhorses of the body, participate in virtually every single process in a cell. Different types of molecules, such as sugars, can be added onto a protein to change its role or location, but this process may also play a role in cancer. Indeed, tumor cells that contain certain sugar modifications are more likely to be able to spread through the body. For example, a specific combination of sugars called T antigen is rarely present in healthy adult cells; yet, it is commonly found in cancer cells that leave the tumor where they were born and invade another tissue to form a new tumor. However, it is not clear whether T antigen actively helps this process inside the body, or is simply present during it. To answer this question, Valoskova, Biebl et al. used genetic and biochemistry tools to study developing fruit fly embryos, where certain immune cells carry T antigen on their proteins. Like invading cancer cells, these immune cells can get inside tissues during development. The experiments revealed that a protein called Minerva helps attach T antigen onto proteins. When embryos were engineered to contain less Minerva, the amount of T antigen in the immune cells dropped, and the cells could not easily make their way into tissues anymore. When the mouse version of Minerva was then added to the embryos, the immune cells of the fruit flies had higher T antigen levels on their proteins and could invade tissues again. Some of the proteins targeted by Minerva were known to be involved in cancer, but not all of them. Future experiments will investigate which role the human version of Minerva plays in cancer cells that get inside new tissues, and if it could help us predict whether a cancer is likely to spread.
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