title: N-linked glycosylation at Asn152 on CD147 affects protein folding and stability: promoting tumour metastasis in hepatocellular carcinoma.
abstract: Cluster of differentiation 147 (CD147), also known as extracellular matrix metalloproteinase inducer, is a transmembrane glycoprotein that mediates oncogenic processes partly through N-glycosylation modifications. N-glycosylation has been demonstrated to be instrumental for the regulation of CD147 function during malignant transformation. However, the role that site-specific glycosylation of CD147 plays in its defective function in hepatocellular carcinomacells needs to be determined. Here, we demonstrate that the modification of N-glycosylation at Asn152 on CD147 strongly promotes hepatocellular carcinoma (HCC) invasion and migration. After the removal of N-glycans at Asn152, CD147 was more susceptible to degradation by ER-localized ubiquitin ligase-mediated endoplasmic reticulum-associated degradation (ERAD). Furthermore, N-linked glycans at Asn152 were required for CD147 to acquire and maintain proper folding in the ER. Moreover, N-linked glycans at Asn152 functioned as a recognition motif that was directly mediated by the CNX quality control system. Two phases in the retention-based ER chaperones system drove ER-localized CD147 trafficking to degradation. Deletion of N-linked glycosylation at Asn152 on CD147 significantly suppressed in situ tumour metastasis. These data could potentially shed light on the molecular regulation of CD147 through glycosylation and provide a valuable means of developing drugs that target N-glycans at Asn152 on CD147.
authors.affiliation: National Translational Science Center for Molecular Medicine, Department of Cell Biology, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Jiang-Hua
authors.initials: JH
authors.lastname: Li
authors.affiliation: National Translational Science Center for Molecular Medicine, Department of Cell Biology, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Wan
authors.initials: W
authors.lastname: Huang
authors.affiliation: National Translational Science Center for Molecular Medicine, Department of Cell Biology, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Lin
authors.affiliation: National Translational Science Center for Molecular Medicine, Department of Cell Biology, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wu
authors.affiliation: National Translational Science Center for Molecular Medicine, Department of Cell Biology, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Zhi-Guang
authors.initials: ZG
authors.lastname: Fu
authors.affiliation: National Translational Science Center for Molecular Medicine, Department of Cell Biology, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Hao-Miao
authors.initials: HM
authors.lastname: Shen
authors.affiliation: National Translational Science Center for Molecular Medicine, Department of Cell Biology, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Jing
authors.affiliation: National Translational Science Center for Molecular Medicine, Department of Cell Biology, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Liu
authors.affiliation: National Translational Science Center for Molecular Medicine, Department of Cell Biology, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: National Translational Science Center for Molecular Medicine, Department of Cell Biology, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Meng
authors.affiliation: National Translational Science Center for Molecular Medicine, Department of Cell Biology, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Bao-Qing
authors.initials: BQ
authors.lastname: Xu
authors.affiliation: National Translational Science Center for Molecular Medicine, Department of Cell Biology, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Zhi-Nan
authors.initials: ZN
authors.lastname: Chen
authors.affiliation: National Translational Science Center for Molecular Medicine, Department of Cell Biology, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Jian-Li
authors.initials: JL
authors.lastname: Jiang
mesh_terms: D000818:Animals; D001216:Asparagine / Q000737:chemistry* / Q000276:immunology; D051926:Basigin / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000276:immunology / Q000556:secondary; D045744:Cell Line, Tumor; D060746:Endoplasmic Reticulum-Associated Degradation; D015972:Gene Expression Regulation, Neoplastic; D006031:Glycosylation; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics* / Q000276:immunology / Q000556:secondary; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D009368:Neoplasm Transplantation; D011134:Polysaccharides / Q000737:chemistry / Q000276:immunology; D017510:Protein Folding; D059748:Proteolysis
chemical_list: C497886:BSG protein, human; D011134:Polysaccharides; D051926:Basigin; D001216:Asparagine