Structural and functional characterization of β2-glycoprotein I domain 1 in anti-melanoma cell migration

Shr Jeng Jim Leu, Tzong Yi Lee, Shu Wei Cheng, Meng Ying Tsai, Yu Shan Lin, Tzeon Jye Chiou, Kai Yao Huang, An Na Chiang

研究成果: 雜誌貢獻文章同行評審

1 引文 斯高帕斯(Scopus)


We previously found that circulating β2-glycoprotein I inhibits human endothelial cell migration, proliferation, and angiogenesis by diverse mechanisms. In the present study, we investigated the antitumor activities of β2-glycoprotein I using structure-function analysis and mapped the critical region within the β2-glycoprotein I peptide sequence that mediates anticancer effects. We constructed recombinant cDNA and purified different β2-glycoprotein I polypeptide domains using a baculovirus expression system. We found that purified β2-glycoprotein I, as well as recombinant β2-glycoprotein I full-length (D12345), polypeptide domains I-IV (D1234), and polypeptide domain I (D1) significantly inhibited melanoma cell migration, proliferation and invasion. Western blot analyses were used to determine the dysregulated expression of proteins essential for intracellular signaling pathways in B16-F10 treated with β2-glycoprotein I and variant recombinant polypeptides. Using a melanoma mouse model, we found that D1 polypeptide showed stronger potency in suppressing tumor growth. Structural analysis showed that fragments A and B within domain I would be the critical regions responsible for antitumor activity. Annexin A2 was identified as the counterpart molecule for β2-glycoprotein I by immunofluorescence and coimmunoprecipitation assays. Interaction between specific amino acids of β2-glycoprotein I D1 and annexin A2 was later evaluated by the molecular docking approach. Moreover, five amino acid residues were selected from fragments A and B for functional evaluation using site-directed mutagenesis, and P11A, M42A, and I55P mutations were shown to disrupt the anti-melanoma cell migration ability of β2-glycoprotein I. This is the first study to show the therapeutic potential of β2-glycoprotein I D1 in the treatment of melanoma progression.

頁(從 - 到)1974-1986
期刊Cancer Science
出版狀態已發佈 - 6月 2019

ASJC Scopus subject areas

  • 腫瘤科
  • 癌症研究


深入研究「Structural and functional characterization of β2-glycoprotein I domain 1 in anti-melanoma cell migration」主題。共同形成了獨特的指紋。