ERβ decreases the invasiveness of triple-negative breast cancer cells by regulating mutant p53 oncogenic function

Igor Bado1, Fotis Nikolos1, Gayani Rajapaksa1

  • 1Department of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, University of Houston, Houston, Texas 77204, USA.

Oncotarget
|February 13, 2016
PubMed

Insights

Wild-type estrogen receptor beta (ERβ1) inhibits triple-negative breast cancer (TNBC) metastasis by blocking mutant p53 activity. This pathway involves p63, revealing a new mechanism to reduce TNBC aggressiveness.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Triple-negative breast cancer (TNBC) often features mutant p53 proteins driving metastasis.
  • Wild-type estrogen receptor beta (ERβ1) is known to reduce TNBC cell invasiveness and epithelial-to-mesenchymal transition (EMT).

Purpose of the Study:

  • To identify the signaling pathways utilized by ERβ1 to inhibit EMT and invasion in TNBC cells.
  • To elucidate the molecular interactions between ERβ1, mutant p53, and p63 in TNBC.

Main Methods:

  • Investigated ERβ1 interactions with mutant p53 and p63.
  • Analyzed the effect of ERβ1 on the transcriptional activity of mutant p53 at metastasis-related gene promoters.
  • Assessed the impact of p63 downregulation on ERβ1-expressing cells and mutant p53 target gene expression.

Main Results:

  • ERβ1 directly binds to and antagonizes the transcriptional activity of mutant p53 at promoters of metastasis-associated genes.
  • p63, which cooperates with mutant p53, also interacts with ERβ1.
  • Reducing p63 levels in ERβ1-expressing cells reverses the epithelial phenotype and modifies mutant p53 target gene expression.

Conclusions:

  • ERβ1 inhibits TNBC aggressiveness by disrupting the oncogenic signaling of mutant p53.
  • ERβ1's mechanism involves direct interaction with mutant p53 and modulation of p63 activity.
  • This study uncovers a novel pathway for targeting TNBC metastasis.

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