A signaling network regulate the O-glycosylation program that controls cell migration

What is it about?

O-glycosylation is normally initiated in the Golgi, but initiation enzymes can be relocated to the ER upon a stimuli, resulting in increased cell motility. By RNAi screening, we identified negative regulators of the relocation, including the ERK8 kinase. ERK8 blocks the incorporation of initiation enzymes in vesicles and thus their flux back to the ER. In human tumors, ERK8 expression is often lost, driving this ER specific glycosylation program and in turn tissue invasion.

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Why is it important?

Virtually all cell surface proteins are regulated by glycosylation. In cancer, O-glycosylation is strongly increased, but the mechanism is unknown. Here we describe how signaling molecules control O-glycosylation through the subcellular location of glycosylation enzymes. This indicates that compartmentation of glycosylation enzymes is a major target of signaling pathways and point to a key mechanism activating protein O-glycosylation in human cancers.