title: Dimerization is essential for HAb18G/CD147 promoting tumor invasion via MAPK pathway.
abstract: HAb18G/CD147 is a transmembrane glycoprotein of the immunoglobulin superfamily (IgSF) and is reported to be correlated with invasion and metastasis of many cancers. The crystal structure of HAb18G/CD147 ectodomain has shown that it can form homodimers in crystal. However, the functional significance of HAb18G/CD147 dimerization remains unclear. In the present study, guided by the crystal structure, we performed extensive mutational and functional studies to identify residues critical for dimerization and molecular function of HAb18G/CD147. Fourteen mutants were purified and evaluated for their ability to form dimers in solution and in living cells. Subsequent functional validation revealed that K63E and S193A mutants, which disrupted CD147 dimerization both in solution and in living cells, showed clearly dominant-negative effects on MAPK activation, MMP2 induction and invasiveness in tumor cells. Taken together, the present study provides mutational and functional evidences demonstrating for the first time the functional importance of CD147 dimerization and its direct correlation with invasion and metastasis of tumor cells.
authors.affiliation: State Key Laboratory of Cancer Biology, Cell Engineering Research Center & Department of Cell Biology, Fourth Military Medical University, Xi'an, China.
authors.forename: Hong-Yong
authors.initials: HY
authors.lastname: Cui
authors.forename: Tao
authors.initials: T
authors.lastname: Guo
authors.forename: Shi-Jie
authors.initials: SJ
authors.lastname: Wang
authors.forename: Pu
authors.initials: P
authors.lastname: Zhao
authors.forename: Zhi-Shou
authors.initials: ZS
authors.lastname: Dong
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
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Yu
mesh_terms: D051926:Basigin / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D009154:Mutation; D009361:Neoplasm Invasiveness; D055503:Protein Multimerization
chemical_list: C497886:BSG protein, human; D051926:Basigin; D020929:Mitogen-Activated Protein Kinase Kinases; D020778:Matrix Metalloproteinase 2