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Updated: Jul 21, 2025

Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
Loss of ANCO1 Expression Regulates Chromatin Accessibility and Drives Progression of Early-Stage Triple-Negative
Meng Yuan1, Megan E Barefoot1, Kendell Peterson1
1Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA.
Abstract:
Mutations in the gene ankyrin repeat domain containing 11 (ANKRD11/ANCO1) play a role in neurodegenerative disorders, and its loss of heterozygosity and low expression are seen in some cancers. Here, we show that low ANCO1 mRNA and protein expression levels are prognostic markers for poor clinical outcomes in breast cancer and that loss of nuclear ANCO1 protein expression predicts lower overall survival of patients with triple-negative breast cancer (TNBC). Knockdown of ANCO1 in early-stage TNBC cells led to aneuploidy, cellular senescence, and enhanced invasion in a 3D matrix. The presence of a subpopulation of ANCO1-depleted cells enabled invasion of the overall cell population in vitro and they converted more rapidly to invasive lesions in a xenograft mouse model. In ANCO1-depleted cells, ChIP-seq analysis showed a global increase in H3K27Ac signals that were enriched for AP-1, TEAD, STAT3, and NFκB motifs. ANCO1-regulated H3K27Ac peaks had a significantly higher overlap with known breast cancer enhancers compared to ANCO1-independent ones. H3K27Ac engagement was associated with transcriptional activation of genes in the PI3K-AKT, epithelial-mesenchymal transition (EMT), and senescence pathways. In conclusion, ANCO1 has hallmarks of a tumor suppressor whose loss of expression activates breast-cancer-specific enhancers and oncogenic pathways that can accelerate the early-stage progression of breast cancer.
Insights
Loss of ANCO1 (ankyrin repeat domain containing 11) expression indicates poor breast cancer prognosis. Its depletion promotes invasion and activates oncogenic pathways, suggesting ANCO1 acts as a tumor suppressor.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Mutations in ANKRD11 (ANCO1) are linked to neurodegenerative disorders.
- Loss of heterozygosity and low ANCO1 expression are observed in certain cancers.
Purpose of the Study:
- To investigate the role of ANCO1 in breast cancer progression.
- To determine if ANCO1 expression levels are prognostic markers for breast cancer outcomes.
Main Methods:
- Analysis of ANCO1 mRNA and protein expression in breast cancer patient samples.
- ANCO1 knockdown in triple-negative breast cancer (TNBC) cells and assessment of cellular phenotypes (aneuploidy, senescence, invasion).
- ChIP-seq analysis to identify regulatory elements and associated transcription factors affected by ANCO1 depletion.
Main Results:
- Low ANCO1 expression is a prognostic marker for poor clinical outcomes in breast cancer, particularly for overall survival in TNBC.
- ANCO1 knockdown induced aneuploidy, senescence, and enhanced invasion in TNBC cells.
- ANCO1 depletion globally increased H3K27Ac signals, enriched for AP-1, TEAD, STAT3, and NFκB motifs, and activated genes in PI3K-AKT, EMT, and senescence pathways.
Conclusions:
- ANCO1 functions as a tumor suppressor in breast cancer.
- Loss of ANCO1 expression activates breast cancer-specific enhancers and oncogenic pathways, accelerating early-stage tumor progression.
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