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Updated: Jul 11, 2025
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
3-D chromatin conformation, accessibility, and gene expression profiling of triple-negative breast cancer
Pere Llinàs-Arias1, Miquel Ensenyat-Méndez1, Javier I J Orozco2
1Cancer Epigenetics Laboratory at the Cancer Cell Biology Group, Health Research Institute of the Balearic Islands (IdISBa), 07120, Palma, Spain.
Objectives:
Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer subtype with limited treatment options. Unlike other breast cancer subtypes, the scarcity of specific therapies and greater frequencies of distant metastases contribute to its aggressiveness. We aimed to find epigenetic changes that aid in the understanding of the dissemination process of these cancers.
Data Description:
Using CRISPR/Cas9, our experimental approach led us to identify and disrupt an insulator element, IE8, whose activity seemed relevant for cell invasion. The experiments were performed in two well-established TNBC cellular models, the MDA-MB-231 and the MDA-MB-436. To gain insights into the underlying molecular mechanisms of TNBC invasion ability, we generated and characterized high-resolution chromatin interaction (Hi-C) and chromatin accessibility (ATAC-seq) maps in both cell models and complemented these datasets with gene expression profiling (RNA-seq) in MDA-MB-231, the cell line that showed more significant changes in chromatin accessibility. Altogether, our data provide a comprehensive resource for understanding the spatial organization of the genome in TNBC cells, which may contribute to accelerating the discovery of TNBC-specific alterations triggering advances for this devastating disease.
Insights
Researchers identified an epigenetic insulator element, IE8, crucial for triple-negative breast cancer (TNBC) cell invasion. Disrupting IE8 offers potential therapeutic targets for this aggressive cancer subtype.
Area of Science:
- Genomics
- Epigenetics
- Cancer Biology
Background:
- Triple-negative breast cancer (TNBC) is an aggressive subtype with limited therapeutic options and frequent metastasis.
- Understanding the epigenetic mechanisms driving TNBC dissemination is critical for developing targeted therapies.
Purpose of the Study:
- To investigate epigenetic alterations contributing to TNBC cell invasion and metastasis.
- To identify specific genomic elements involved in the dissemination process of TNBC.
Main Methods:
- Utilized CRISPR/Cas9 to identify and disrupt the insulator element IE8 in TNBC cell models (MDA-MB-231, MDA-MB-436).
- Generated high-resolution chromatin interaction (Hi-C), chromatin accessibility (ATAC-seq), and gene expression (RNA-seq) maps.
- Analyzed multi-omics data to understand the spatial genome organization and molecular mechanisms of TNBC invasion.
Main Results:
- Identified and functionally disrupted the insulator element IE8, demonstrating its relevance in TNBC cell invasion.
- Generated comprehensive epigenetic and transcriptomic datasets for TNBC cell models.
- Revealed significant changes in chromatin accessibility associated with TNBC cell invasion.
Conclusions:
- The insulator element IE8 plays a role in TNBC cell invasion, presenting a potential therapeutic target.
- The generated multi-omics data provide a valuable resource for future TNBC research.
- Further investigation into IE8 and associated epigenetic changes may accelerate the discovery of novel TNBC treatments.
