ArticleCancer research2019
Acetylation of CCAR2 Establishes a BET/BRD9 Acetyl Switch in Response to Combined Deacetylase and Bromodomain Inhibition.
Article in Cancer research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Epigenetic regulation of major histocompatibility complexes in gastrointestinal malignancies and the potential for clinical interception.Clinical epigenetics · 2024Pooled it
- Epigenetic Modulators and Immunotherapy in Malignant Melanoma.Oncology research · 2026Review
- Development of Primary Colon and Duodenal Tumor Cultures from the Apc-mutant Pirc Rat for Screening Preventive Agents.Journal of cancer prevention · 2025Article
- Antitumor efficacy of intermittent low-dose erlotinib plus sulindac via MHC upregulation and remodeling of the immune cell niche.International journal of cancer · 2025Article
- Alternative splicing of BAZ1A in colorectal cancer disrupts the DNA damage response and increases chemosensitization.Cell death & disease · 2024Article
- Multifaceted roles of CCAR family proteins in the DNA damage response and cancer.Experimental & molecular medicine · 2024Review
- Histone Acyl Code in Precision Oncology: Mechanistic Insights from Dietary and Metabolic Factors.Nutrients · 2024Review
- Targeting ACE2-BRD4 crosstalk in colorectal cancer and the deregulation of DNA repair and apoptosis.NPJ precision oncology · 2023Article
- PROTACs in gastrointestinal cancers.Molecular therapy oncolytics · 2022Review
- BRD9 Inhibition by Natural Polyphenols Targets DNA Damage/Repair and Apoptosis in Human Colon Cancer Cells.Nutrients · 2022Article
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- Article
- Translational Advances in Cancer Prevention Agent Development (TACPAD) Virtual Workshop on Immunomodulatory Agents: Report.Journal of cancer prevention · 2021Article
- BRD9 is a druggable component of interferon-stimulated gene expression and antiviral activity.EMBO reports · 2021Article
- Meeting Report: Translational Advances in Cancer Prevention Agent Development Meeting.Journal of cancer prevention · 2021Article
- Deacetylase Plus Bromodomain Inhibition Downregulates ERCC2 and Suppresses the Growth of Metastatic Colon Cancer Cells.Cancers · 2021Article
- Optimization of Erlotinib Plus Sulindac Dosing Regimens for Intestinal Cancer Prevention in an Apc-Mutant Model of Familial Adenomatous Polyposis (FAP).Cancer prevention research (Philadelphia, Pa.) · 2021Article
- Targeting Epigenetic 'Readers' with Natural Compounds for Cancer Interception.Journal of cancer prevention · 2020Review
- Emerging crosstalk between long non-coding RNAs and Nrf2 signaling.Cancer letters · 2020Article
- CCAR1 and CCAR2 as gene chameleons with antagonistic duality: Preclinical, human translational, and mechanistic basis.Cancer science · 2020Review
Corrections and comments
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Authors and funding
21 authors at 5 institutions in 1 country.
Funding
Abstract
There continues to be interest in targeting epigenetic "readers, writers, and erasers" for the treatment of cancer and other pathologies. However, a mechanistic understanding is frequently lacking for the synergy observed when combining deacetylase and bromodomain inhibitors. Here we identify cell cycle and apoptosis regulator 2 (CCAR2) as an early target for acetylation in colon cancer cells treated with sulforaphane. N-terminal acetylation of CCAR2 diminished its interactions with histone deacetylase 3 and β-catenin, interfering with Wnt coactivator functions of CCAR2, including in cells harboring genetically encoded CCAR2 acetylation. Protein domain arrays and pull-down assays identified acetyl "reader" proteins that recognized CCAR2 acetylation sites, including BRD9 and members of the bromodomain and extraterminal domain (BET) family. Treatment with the BET inhibitor JQ1 synergized with sulforaphane in colon cancer cells and suppressed tumor development effectively in a preclinical model of colorectal cancer. Studies with sulforaphane+JQ1 in combination implicated a BET/BRD9 acetyl switch and a shift in the pool of acetyl "reader" proteins in favor of BRD9-regulated target genes. SIGNIFICANCE: These results highlight the competition that exists among the "readers" of acetylated histone and nonhistone proteins and provide a mechanistic basis for potential new therapeutic avenues involving epigenetic combination treatments.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.