Dickkopf-1 enhances migration of HEK293 cell by beta-catenin/E-cadherin degradation

Front Biosci (Landmark Ed). 2009 Jan 1;14:2212-20. doi: 10.2741/3373.

Abstract

Migration is an important process during cellular activity and embryo development. We recently showed that Dickkopf-1(Dkk-1), an antagonist of Wnt/ beta-catenin signaling pathway, could promote trophoblast cell invasion during murine placentation. However, mechanism of Dkk-1 action on cell migration was not clear. The objective of this study was to further evaluate the effect of Dkk-1 on cell migration and to identify the underlining mechanisms. Functional assays with stable Dkk-1 transfected HEK293 cells revealed that Dkk-1 expression increased cell migration by decreasing cell-cell adhesion, not cell-matrix adhesion. Treatment with LiCl and Genistein (widely used inhibitor of glycogen synthase kinase-3 and tyrosine protein kinase, respectively.) could inhibit the migration effect of Dkk-1, and significantly increased the membrane localization of beta-catenin and E-cadherin in HEK293 cells transfected with Dkk-1. Further data showed that HEK293 cells transfected with Dkk-1 have significantly decreased accumulation of both beta-catenin and E-cadherin at the cell membrane. Together, our data suggest that Dkk-1 stimulates the release of beta-catenin from cell membrane and facilitates cell migration which accompanies degradation of beta-catenin/E-cadherin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Blotting, Western
  • Cadherins / metabolism*
  • Cell Cycle
  • Cell Line
  • Cell Movement / drug effects
  • Cell Movement / physiology*
  • Fluorescent Antibody Technique
  • Genistein / pharmacology
  • Humans
  • Hydrolysis
  • Intercellular Signaling Peptides and Proteins / physiology*
  • Lithium Chloride / pharmacology
  • beta Catenin / metabolism*

Substances

  • Cadherins
  • DKK1 protein, human
  • Intercellular Signaling Peptides and Proteins
  • beta Catenin
  • Genistein
  • Lithium Chloride