کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1929125 | 1050446 | 2012 | 6 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Domain 5 of high molecular weight kininogen inhibits collagen-mediated cancer cell adhesion and invasion in association with α-actinin-4 Domain 5 of high molecular weight kininogen inhibits collagen-mediated cancer cell adhesion and invasion in association with α-actinin-4](/preview/png/1929125.png)
High molecular weight kininogen (HK) is a plasma glycoprotein with multiple functions, including the regulation of coagulation. We previously demonstrated that domain 5 (D5H), a functional domain of HK, and its derived peptides played an important role in the vitronectin-mediated suppression of cancer cell adhesion and invasion. However, the underlying mechanisms of the D5H-mediated suppressive effects remain to be elucidated. Here, we showed that D5H and its derivatives inhibited the collagen-mediated cell adhesion and invasion of human osteosarcoma MG63 cells. Using purified D5H fused to glutathione-S-transferase (GST) and D5H-derived peptides for column chromatography, an actin-binding protein, α-actinin-4, was identified as a binding protein of D5H with high-affinity for P-5m, a core octapeptide of D5H. Immunofluorescence microscopy demonstrated that D5H co-localized with α-actinin-4 inside MG63 cells. In addition, exogenous GST-D5H added to the culture media was transported into MG63 cells, although GST alone as a control was not. As α-actinin-4 regulates actin polymerization necessary for cell adhesion and is related to the integrin-dependent attachment of cells to the extracellular matrix, our results suggest that D5H may modulate cell adhesion and invasion together with actinin-4.
► Collagen-mediated cell adhesion and invasion of MG63 cells was inhibited by D5H.
► Similar effects were observed using D5H-derived peptides.
► α-Actinin-4 is a binding protein of D5H with high-affinity for P-5m.
► D5H was transported into MG63 cells and co-localized with α-actinin-4.
Journal: Biochemical and Biophysical Research Communications - Volume 427, Issue 3, 26 October 2012, Pages 497–502