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Assays for Validating Histone Acetyltransferase Inhibitors
Published on: August 6, 2020
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Quantitative Analysis of Cell Aggregation Dynamics Identifies HDAC Inhibitors as Potential Regulators of Cancer Cell
Fabien Gava1, Julie Pignolet1, Sébastien Déjean2
1Institut des Technologies Avancées en Sciences du Vivant (ITAV)-USR3505, Université de Toulouse, CNRS, Université Paul Sabatier, 31100 Toulouse, France.
Cancers
|November 27, 2021
Summary
Understanding tumor cell clustering mechanisms can lead to new cancer therapies. Histone deacetylase (HDAC) inhibitors were found to significantly reduce tumor cell aggregation, offering potential to prevent metastasis.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Tumor cell clustering is a critical step in metastasis.
- Understanding the molecular drivers of cell aggregation is key to developing anti-metastatic therapies.
Purpose of the Study:
- To identify molecular mechanisms regulating cancer cell aggregation.
- To explore the potential of targeting these mechanisms for therapeutic intervention.
Main Methods:
- Quantitative in vitro assay to monitor anchorage-independent cancer cell aggregation kinetics across 25 cell lines.
- Analysis of gene expression data (CCLE database) correlated with aggregation parameters.
- Comparison with perturbagen signatures (Connectivity Map) to identify drug targets.
Main Results:
- Identified specific genes significantly associated with variations in cancer cell aggregation dynamics.
- Found a strong correlation between these genes and the transcriptional signatures of histone deacetylase (HDAC) inhibitors.
- Experimental validation confirmed that two HDAC inhibitors (SAHA, ISOX) inhibit initial tumor cell aggregation in vitro.
Conclusions:
- Molecular mechanisms underlying tumor cell clustering are linked to HDAC inhibitor activity.
- HDAC inhibitors show promise as a therapeutic strategy to inhibit cancer cell aggregation and prevent metastasis.
