Dickkopf-1 enhances migration of HEK293 cell by beta-catenin/E-cadherin degradation.
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.
Kuang
Hai-Bin
HB
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, P.R. China.
Miao
Cheng-Lin
CL
Guo
Wei-Xiang
WX
Peng
Sha
S
Cao
Yu-Jing
YJ
Duan
En-Kui
EK
D017209:Apoptosis; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism*; D002453:Cell Cycle; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D006868:Hydrolysis; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D018021:Lithium Chloride / Q000494:pharmacology; D051176:beta Catenin / Q000378:metabolism*
D015820:Cadherins; C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D051176:beta Catenin; D019833:Genistein; D018021:Lithium Chloride