Human natural killer-1 sulfotransferase (HNK-1ST)-induced sulfate transfer regulates laminin-binding glycans on α-dystroglycan.
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 α-dystroglycan (α-DG) in RA-treated S91 melanoma cells, which contributed to an attenuation of cell migration. Knockdown of HNK-1ST restored the glycosylation of α-DG and the migration of RA-treated S91 cells, indicating that HNK-1ST functions through glycans on α-DG. Using CHO-K1 cells, we provide direct evidence that HNK-1ST but not other homologous sulfotransferases (C4ST1 and GalNAc4ST1) suppresses the glycosylation of α-DG. The activity-abolished mutant of HNK-1ST did not show the α-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 α-DG. These findings suggest a novel role for HNK-1ST as a tumor suppressor controlling the functional glycans on α-DG and the importance of sulfate transfer in the glycosylation of α-DG.
Department of Biological Chemistry, Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507, Japan.
Naoki
N
Nakagawa
Hiroshi
H
Manya
Tatsushi
T
Toda
Tamao
T
Endo
Shogo
S
Oka
D000818:Animals; D016466:CHO Cells; D002465:Cell Movement / Q000235:genetics; D006224:Cricetinae; D003412:Cricetulus; D049030:Dystroglycans / Q000235:genetics / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D007797:Laminin / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D011134:Polysaccharides / Q000235:genetics / Q000378:metabolism*; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D000097811:Carbohydrate Sulfotransferases
D049030:Dystroglycans; D007797:Laminin; D011134:Polysaccharides; D015238:Sulfotransferases; D025521:Tumor Suppressor Proteins; C499549:CHST10 protein, human; D000097811:Carbohydrate Sulfotransferases