Human natural killer-1 sulfotransferase (HNK-1ST)-induced sulfate transfer regulates laminin-binding glycans on ?-dystroglycan.

ABSTRACT: Retinoic acid (RA) is a well established anti-tumor agent inducing differentiation in various cancer cells. Recently, a robust up-regulation of human natural killer-1 sulfotransferase (HNK-1ST) was found in several subsets of melanoma cells during RA-mediated differentiation. However, the molecular mechanism underlying the tumor suppression mediated by HNK-1ST remains unclear. Here, we show that HNK-1ST changed the glycosylation state and reduced the ligand binding activity of ?-dystroglycan (?-DG) in RA-treated S91 melanoma cells, which contributed to an attenuation of cell migration. Knockdown of HNK-1ST restored the glycosylation of ?-DG and the migration of RA-treated S91 cells, indicating that HNK-1ST functions through glycans on ?-DG. Using CHO-K1 cells, we provide direct evidence that HNK-1ST but not other homologous sulfotransferases (C4ST1 and GalNAc4ST1) suppresses the glycosylation of ?-DG. The activity-abolished mutant of HNK-1ST did not show the ?-DG-modulating function, indicating that the sulfotransferase activity of HNK-1ST is essential. Finally, the HNK-1ST-dependent incorporation of [(35)S]sulfate groups was detected on ?-DG. These findings suggest a novel role for HNK-1ST as a tumor suppressor controlling the functional glycans on ?-DG and the importance of sulfate transfer in the glycosylation of ?-DG.

SUBMITTER: Nakagawa N 

PROVIDER: S-EPMC3436325 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature