J Biol Chem 2005,
PMID: 15509575
Endo, Yoshimi; Wolf, Vladimir; Muraiso, Kanae; Kamijo, Keiju; Soon, Lilian; Uren, Aykut; Barshishat-Küpper, Michal; Rubin, Jeffrey S
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 beta-catenin, two inhibitors of the beta-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 beta-catenin signaling, inhibition of Rho kinase partially blocked motility. Because Dishevelled (Dvl) proteins are effectors of both canonical and noncanonical Wnt signaling, we used immunofluorescent 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.
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Text Mining Data
RhoA → dishevelled-2: "
Wnt-3a dependent cell motility involves
RhoA activation and is specifically
regulated by
dishevelled-2
"
beta-catenin → Wnt-3a: "
Although Wnt-3a stabilized beta-catenin , two inhibitors of the beta-catenin/canonical pathway, Dickkopf-1 and a dominant negative T cell factor construct, did not reduce motility
"
RhoA → Wnt-3a: "
The small GTPase RhoA also was activated by Wnt-3a
"
Manually curated Databases
-
NCI Pathway Database Noncanonical Wnt signaling pathway:
None
→
RHOA/GTP complex (RHOA)
(modification, collaborate)
Evidence: mutant phenotype
-
NCI Pathway Database Noncanonical Wnt signaling pathway:
None
→
DVL/DAAM1 complex (DVL3_DVL1_DVL2-DAAM1)
(modification, collaborate)
Evidence: mutant phenotype
-
NCI Pathway Database Noncanonical Wnt signaling pathway:
None
→
RHOA/GDP complex (RHOA)
(modification, collaborate)
Evidence: mutant phenotype
-
NCI Pathway Database Noncanonical Wnt signaling pathway:
None
→
None
(modification, collaborate)
Evidence: mutant phenotype
-
NCI Pathway Database Noncanonical Wnt signaling pathway:
RHOA/GTP complex (RHOA)
→
RHOA/GDP complex (RHOA)
(modification, collaborate)
Evidence: mutant phenotype
-
NCI Pathway Database Noncanonical Wnt signaling pathway:
RHOA/GTP complex (RHOA)
→
None
(modification, collaborate)
Evidence: mutant phenotype
-
NCI Pathway Database Noncanonical Wnt signaling pathway:
DVL/DAAM1 complex (DVL3_DVL1_DVL2-DAAM1)
→
RHOA/GDP complex (RHOA)
(modification, activates)
Evidence: mutant phenotype
-
NCI Pathway Database Noncanonical Wnt signaling pathway:
DVL/DAAM1 complex (DVL3_DVL1_DVL2-DAAM1)
→
None
(modification, activates)
Evidence: mutant phenotype
-
NCI Pathway Database Noncanonical Wnt signaling pathway:
RHOA/GDP complex (RHOA)
→
None
(modification, collaborate)
Evidence: mutant phenotype
-
NCI Pathway Database Wnt signaling network:
WNT3A (WNT3A)
→
FZD1 (FZD1)
(modification, collaborate)
Evidence: mutant phenotype
-
NCI Pathway Database Wnt signaling network:
WNT3A (WNT3A)
→
WNT3A/FZD1 complex (WNT3A-FZD1)
(modification, collaborate)
Evidence: mutant phenotype
-
NCI Pathway Database Wnt signaling network:
FZD1 (FZD1)
→
WNT3A/FZD1 complex (WNT3A-FZD1)
(modification, collaborate)
Evidence: mutant phenotype
In total, 11 gene pairs are associated to this article in curated databases