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Updated: Mar 25, 2026

Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence
Published on: December 30, 2025
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.
Abstract:
Most (80%) of the triple-negative breast cancers (TNBCs) express mutant p53 proteins that acquire oncogenic activities including promoting metastasis. We previously showed that wild-type ERβ (ERβ1) impedes epithelial to mesenchymal transition (EMT) and decreases the invasiveness of TNBC cells. In the present study we searched for signaling pathways that ERβ1 uses to inhibit EMT and invasion in TNBC cells. We show that ERβ1 binds to and opposes the transcriptional activity of mutant p53 at the promoters of genes that regulate metastasis. p63 that transcriptionally cooperates with mutant p53 also binds to ERβ1. Downregulation of p63 represses the epithelial phenotype of ERβ1-expressing cells and alters the expression of mutant p53 target genes. These results describe a novel mechanism through which ERβ1 can disturb oncogenic signals to inhibit aggressiveness in TNBCs.
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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