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Dvl2-dependent activation of Daam1 and RhoA regulates Wnt5a-induced breast cancer cell migration.


ABSTRACT:

Background

The Dishevelled (Dvl) and Dishevelled-associated activator of morphogenesis 1 (Daam1) pathway triggered by Wnt5a regulates cellular polarity during development and tissue homoeostasis. However, Wnt5a signaling in breast cancer progression remains poorly defined.

Methodology/principal findings

We showed here that Wnt5a activated Dvl2, Daam1 and RhoA, and promoted migration of breast cancer cells, which was, however, abolished by Secreted Frizzled-related protein 2 (sFRP2) pretreatment. Dominant negative Dvl2 mutants or Dvl2 siRNA significantly decreased Wnt5a-induced Daam1/RhoA activation and cell migration. Ectopic expression of N-Daam1, a dominant negative mutant, or Daam1 siRNA remarkably inhibited Wnt5a-induced RhoA activation, stress fiber formation and cell migration. Ectopic expression of dominant negative RhoA (N19) or C3 exoenzyme transferase, a Rho inhibitor, decreased Wnt5a-induced stress fiber formation and cell migration.

Conclusions/significance

Taken together, we demonstrated for the first time that Wnt5a promotes breast cancer cell migration via Dvl2/Daam1/RhoA.

SUBMITTER: Zhu Y 

PROVIDER: S-EPMC3360006 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

Dvl2-dependent activation of Daam1 and RhoA regulates Wnt5a-induced breast cancer cell migration.

Zhu Yichao Y   Tian Yinhui Y   Du Jun J   Hu Zhenzhen Z   Yang Ling L   Liu Jiaojing J   Gu Luo L  

PloS one 20120524 5


<h4>Background</h4>The Dishevelled (Dvl) and Dishevelled-associated activator of morphogenesis 1 (Daam1) pathway triggered by Wnt5a regulates cellular polarity during development and tissue homoeostasis. However, Wnt5a signaling in breast cancer progression remains poorly defined.<h4>Methodology/principal findings</h4>We showed here that Wnt5a activated Dvl2, Daam1 and RhoA, and promoted migration of breast cancer cells, which was, however, abolished by Secreted Frizzled-related protein 2 (sFRP2  ...[more]

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