The
dystrophin-
glycoprotein complex connects the cytoskeleton with base membrane components such as
laminin through unique O-
glycans displayed on α-
dystroglycan (α-DG). Genetic impairment of elongation of these
glycans causes congenital
muscular dystrophies. We previously identified that
glycerol phosphate (GroP) can cap the core part of the α-DG O-
glycans and terminate their further elongation. This study examined the possible roles of the GroP modification in
cancer malignancy, focusing on
colorectal cancer. We found that the GroP modification critically depends on PCYT2, which serves as
cytidine 5'-diphosphate-glycerol (
CDP-Gro) synthase. Furthermore, we identified a significant positive correlation between
cancer progression and GroP modification, which also correlated positively with PCYT2 expression. Moreover, we demonstrate that GroP modification promotes the migration of
cancer cells. Based on these findings, we propose that the GroP modification by PCYT2 disrupts the
glycan-mediated cell adhesion to the extracellular matrix and thereby enhances
cancer metastasis. Thus, the present study suggests the possibility of novel approaches for
cancer treatment by targeting the PCYT2-mediated GroP modification.