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DDB2: a novel regulator of NF-κB and breast tumor invasion

Marie Ennen1, Rémi Klotz, Nadège Touche

  • 1Centre de Recherche en Automatique de Nancy (CRAN), UMR 7039 Centre National de la Recherche Scientifique (CNRS), Université de Lorraine, Faculté des Sciences et Technologies, Cedex, France.

Cancer Research
|June 19, 2013
PubMed

Insights

Overexpression of the DNA repair protein damaged DNA-binding 2 (DDB2) inhibits breast cancer cell invasion and metastasis. DDB2 may serve as a therapeutic target to block malignant progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The DNA repair protein damaged DNA-binding 2 (DDB2) is known to regulate gene expression and cell-cycle progression.
  • DDB2 is selectively overexpressed in noninvasive breast tumor cells, but not in invasive ones.

Purpose of the Study:

  • To investigate the role of DDB2 in breast cancer cell invasion and metastasis.
  • To elucidate the molecular mechanisms by which DDB2 affects malignant progression.

Main Methods:

  • Studied the effect of DDB2 overexpression on human breast tumor cell motility and invasiveness in vitro.
  • Assessed the ability of DDB2-overexpressing cells to colonize lungs in vivo.
  • Investigated the impact of DDB2 on NF-κB activity and MMP9 expression.
  • Examined the mechanism of DDB2-mediated regulation of IκBα expression.

Main Results:

  • DDB2 overexpression in invasive breast tumor cells limited their motility and invasiveness in vitro and reduced lung colonization in vivo.
  • DDB2 overexpression attenuated NF-κB activity and decreased MMP9 expression.
  • DDB2 upregulated IκBα expression by binding to its promoter, thereby decreasing NF-κB activity.
  • Knockdown of DDB2 restored NF-κB activity, MMP9 expression, and invasive properties.

Conclusions:

  • DDB2 plays a novel role in suppressing malignant progression of breast cancer by inhibiting cell motility and invasiveness.
  • DDB2 exerts its function by upregulating IκBα, leading to the suppression of NF-κB signaling and MMP9 expression.
  • DDB2 represents a potential prognostic marker and therapeutic target for breast cancer.

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