Initiation of GalNAc-type O-glycosylation in the endoplasmic reticulum promotes cancer cell invasiveness

Significance How cancer cells become invasive is key to understanding malignancy. Perturbations in O-glycosylation are strongly correlated with invasiveness. Here we report that tumor cells display relocation of O-glycosylation initiating glycosyltransferases from the Golgi apparatus to the endoplasmic reticulum (ER). ER-located O-glycosylation stimulates cell migration and invasiveness, which depend on cell surface O-glycoproteins. Inhibition of the glycosyltransferases in the ER reduces tissue invasion and metastasis formation in mice. Our study suggests that control of glycosylation via the subcellular localization of glycosyltransferases is a critical mechanism driving invasiveness in tumor cells.