DDX3 modulates cell adhesion and motility and cancer cell metastasis via Rac1-mediated signaling pathway

H-H Chen1, H-I Yu1, W-C Cho1

  • 1Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.

Oncogene
|July 22, 2014
PubMed

Insights

The DEAD-box RNA helicase DDX3 protein regulates cell adhesion and migration. DDX3 depletion reduces tumor invasion and metastasis by affecting Rac1 and β-catenin signaling, offering insights into Wnt-type medulloblastoma.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • The DEAD-box RNA helicase DDX3 is crucial for gene expression and cellular signaling.
  • Mutations in DDX3 are linked to wingless (Wnt)-type medulloblastoma.
  • Understanding DDX3's role in cell adhesion, migration, and Wnt signaling is vital for cancer therapy.

Purpose of the Study:

  • To investigate the function of DDX3 in cell adhesion, motility, and invasion.
  • To elucidate the molecular mechanisms by which DDX3 regulates cell migration and Wnt/β-catenin signaling.
  • To provide a mechanistic understanding of DDX3's role in Wnt-type medulloblastoma.

Main Methods:

  • Small interfering RNA (siRNA)-mediated DDX3 knockdown in various cell lines.
  • Cell-cell and cell-extracellular matrix adhesion assays.
  • Wound-healing and invasion assays (in vitro and in vivo).
  • Western blotting to assess protein levels (Rac1, β-catenin).
  • Analysis of β-catenin target gene expression and Rac1 mRNA translation.

Main Results:

  • DDX3 knockdown increased cell-cell adhesion but decreased cell-extracellular matrix adhesion.
  • DDX3 depletion suppressed cell motility, directional migration, and invasive capacities.
  • DDX3 knockdown reduced Rac1 and β-catenin protein levels, downregulating β-catenin target genes.
  • DDX3 regulates Rac1 mRNA translation and affects β-catenin protein stability in a Rac1-dependent manner.

Conclusions:

  • DDX3 plays a significant role in regulating cell adhesion, migration, and invasion.
  • The DDX3-Rac1-β-catenin axis is a key regulatory pathway for Wnt/β-catenin target gene expression.
  • This study provides a mechanistic framework for DDX3's involvement in Wnt-type medulloblastoma, highlighting potential therapeutic targets.

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