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Sökning: onr:"swepub:oai:DiVA.org:liu-141658" > Dkk-1 inhibits inte...

Dkk-1 inhibits intestinal epithelial cell migration by attenuating directional polarization of leading edge cells

Koch, Stefan (författare)
Epithelial Pathobiology Unit, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA
Capaldo, Christopher T. (författare)
Epithelial Pathobiology Unit, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA
Samarin, Stanislav (författare)
Epithelial Pathobiology Unit, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA
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Nava, Porfirio (författare)
Epithelial Pathobiology Unit, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA
Neumaier, Irmgard (författare)
Biologische Chemie, Technische Universitaet Muenchen, D-85350 Freising-Weihenstephan, Germany
Skerra, Arne (författare)
Biologische Chemie, Technische Universitaet Muenchen, D-85350 Freising-Weihenstephan, Germany
Sacks, David B. (författare)
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
Parkos, Charles A. (författare)
Epithelial Pathobiology Unit, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA
Nusrat, Asma (författare)
Epithelial Pathobiology Unit, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA
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 (creator_code:org_t)
Bethesda, United States : American Society for Cell Biology, 2009
2009
Engelska.
Ingår i: Molecular Biology of the Cell. - Bethesda, United States : American Society for Cell Biology. - 1059-1524 .- 1939-4586. ; 20:22, s. 4816-4825
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • Wnt signaling pathways regulate proliferation, motility, and survival in a variety of human cell types. Dickkopf-1 (Dkk-1) is a secreted Wnt antagonist that has been proposed to regulate tissue homeostasis in the intestine. In this report, we show that Dkk-1 is secreted by intestinal epithelial cells after wounding and that it inhibits cell migration by attenuating the directional orientation of migrating epithelial cells. Dkk-1 exposure induced mislocalized activation of Cdc42 in migrating cells, which coincided with a displacement of the polarity protein Par6 from the leading edge. Consequently, the relocation of the microtubule organizing center and the Golgi apparatus in the direction of migration was significantly and persistently inhibited in the presence of Dkk-1. Small interfering RNA-induced down-regulation of Dkk-1 confirmed that extracellular exposure to Dkk-1 was required for this effect. Together, these data demonstrate a novel role of Dkk-1 in the regulation of directional polarization of migrating intestinal epithelial cells, which contributes to the effect of Dkk-1 on wound closure in vivo.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Nyckelord

Adaptor Proteins
Signal Transducing/genetics/metabolism
Animals
Apoptosis/physiology
Caco-2 Cells
Cell Movement/*physiology
*Cell Polarity
Cell Proliferation
*Epithelial Cells/cytology/physiology
Golgi Apparatus/metabolism
Humans
Intercellular Signaling Peptides and Proteins/genetics/*metabolism
Intestinal Mucosa/cytology
Microtubule-Organizing Center/metabolism
Wnt Proteins/genetics/metabolism
cdc42 GTP-Binding Protein/genetics/metabolism

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