title: Modulation of CD147-induced matrix metalloproteinase activity: role of CD147 N-glycosylation.
abstract: Degradation of the basement membrane by MMPs (matrix metalloproteinases) is one of the most critical steps in tumour progression. CD147 is a tumour-associated antigen that plays a key regulatory role for MMP activities. In the present study, mass spectrum analysis demonstrated that the purified native CD147 from human lung cancer tissue was N-glycosylated and contained a series of high-mannose and complex-type N-linked glycan structures. Moreover, native glycosylated CD147 existed exclusively as oligomers in solution and directly stimulated MMP production more efficiently than non-glycosylated prokaryotic CD147. The glycosylation site mutation results indicated that, among three N-glycan attachment sites, the N152Q mutants were retained in the endoplasmic reticulum and unfolded protein response signalling was activated. This improper intracellular accumulation impaired its MMP-inducing activity. Increased β1,6-branching of N-glycans as a result of overexpression of GnT-V (N-acetylglucosaminyltransferase V) plays an important role in tumour metastasis. In the present study, we identified CD147 as a target protein of GnT-V and found that overexpression of GnT-V resulted in an elevated level of CD147 at the plasma membrane and in cell-conditioned medium, thereby increasing the induction of MMPs. The present study reveals the important role of N-glycosylation of CD147 in its biological function and implied that targeting aberrant β1,6-branching of N-glycans on CD147 would be valuable for the development of novel therapeutic modalities against carcinoma.
authors.affiliation: Cell Engineering Research Center and Department of Cell Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an, Shaanxi Province 710032, People's Republic of China.
authors.forename: Wan
authors.initials: W
authors.lastname: Huang
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: Luo
authors.forename: Ping
authors.initials: P
authors.lastname: Zhu
authors.forename: Juan
authors.initials: J
authors.lastname: Tang
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Yu
authors.forename: Hong-Yong
authors.initials: HY
authors.lastname: Cui
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jian-Li
authors.initials: JL
authors.lastname: Jiang
authors.forename: Zhi-Nan
authors.initials: ZN
authors.lastname: Chen
mesh_terms: D051926:Basigin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D017077:Culture Media, Conditioned / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006031:Glycosylation; D056945:Hep G2 Cells; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism; D008358:Mannose / Q000737:chemistry / Q000378:metabolism; D013058:Mass Spectrometry; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D018613:Microscopy, Confocal; D009154:Mutation; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism*; D011134:Polysaccharides / Q000737:chemistry / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D056811:Unfolded Protein Response
chemical_list: C497886:BSG protein, human; D017077:Culture Media, Conditioned; D011134:Polysaccharides; D051926:Basigin; D017351:N-Acetylglucosaminyltransferases; C052254:alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D008358:Mannose