title: GP73 N-glycosylation at Asn144 reduces hepatocellular carcinoma cell motility and invasiveness.
abstract: Golgi Protein 73 (GP73) is a potential liver disease glycobiomarker warranting comprehensive analyses of its glycan structure and glycosylation function. In this study, we used mass spectrometry to identify glycosylation sites and the glycan structure, high-throughput lectin microarray to provide rapid and sensitive profiling of glycoconjugates, and site-directed mutagenesis to clarify the impact of glycans on target glycoproteins in vivo. We identified three GP73 N-glycosylation sites: Asn109, Asn144 and Asn398. We found five glycoforms on Asn144, including biantennary, triantennary and fucosylated glycans. Removal of N-glycans at Asn144 enhanced the motility and invasiveness of hepatocellular carcinoma cells, possibly due to inhibition of cell adhesion related to the changes of cell membrane glycosylation. This study increases our understanding of the functional relevance of GP73 glycosylation and suggests that Asn144-deleted GP73 can influence the progression and metastasis of hepatocellular carcinoma.
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China.|Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Jiang
authors.affiliation: Cancer Research Center, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Cancer Research Center, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Qinle
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Cancer Research Center, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Guoquan
authors.initials: G
authors.lastname: Yan
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Guo
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China.|Cancer Research Center, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Yinkun
authors.initials: Y
authors.lastname: Liu
mesh_terms: D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D006031:Glycosylation; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D037102:Lectins / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D011134:Polysaccharides / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: C410824:GOLM1 protein, human; D037102:Lectins; D008565:Membrane Proteins; D011134:Polysaccharides
keywords: Golgi protein 73; N-glycan; hepatocellular carcinoma