Wnt-3a-dependent cell motility involves RhoA activation and is specifically regulated by dishevelled-2

Yoshimi Endo, Vladimir Wolf, Kanae Muraiso, Keiju Kamijo, Lilian Soon, Aykut Üren, Michal Barshishat-Küpper, Jeffrey S. Rubin

Research output: Contribution to journalArticlepeer-review

84 Citations (Scopus)

Abstract

Wnts stimulate cell migration, although the mechanisms responsible for this effect are not fully understood. To investigate the pathways that mediate Wnt-dependent cell motility, we treated Chinese hamster ovary cells with Wnt-3a-conditioned medium and monitored changes in cell shape and movement. Wnt-3a induced cell spreading, formation of protrusive structures, reorganization of stress fibers and migration. Although Wnt-3a stabilized β-catenin, two inhibitors of the β-catenin/canonical pathway, Dickkopf-1 and a dominant-negative T cell factor construct, did not reduce motility. The small GTPase RhoA also was activated by Wnt-3a. In contrast to β-catenin signaling, inhibition of Rho kinase partially blocked motility. Because Dishevelled (Dvl) proteins are effectors of both canonical and noncanonical Wnt signaling, we used immmaofluorescent analysis and small interference RNA technology to evaluate the role of Dvl in cell motility. Specific knock-down of Dvl-2 expression markedly reduced Wnt-3a-dependent changes in cell shape and movement, suggesting that this Dvl isoform had a predominant role in mediating Wnt-3a-dependent motility in Chinese hamster ovary cells.

Original languageEnglish
Pages (from-to)777-786
Number of pages10
JournalJournal of Biological Chemistry
Volume280
Issue number1
DOIs
Publication statusPublished - 2005 Jan 7

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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