ArticleCellular oncology (Dordrecht, Netherlands)2020
BRD4 modulates vulnerability of triple-negative breast cancer to targeting of integrin-dependent signaling pathways.
Article in Cellular oncology (Dordrecht, Netherlands), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- Bridging BET bromodomain and immune checkpoint inhibitors through generative bioorganic frameworks for next-generation cancer immunotherapy.RSC medicinal chemistry · 2026Review
- Article
- ITGB1 Regulates Triple-Negative Breast Cancer Development by Modulating the Tumor Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Focal Adhesion Kinase Intersects With the BRD4-MYC Axis and YAP1 to Drive Tumor Cell Growth, Phenotypic Plasticity, Stemness, and Metastatic Potential in Colorectal Cancer.Cancer medicine · 2025Article
- Androgen-induced AR-BRD4 transcriptional regulatory complex promotes malignant proliferation of osteosarcoma cells.Cell death discovery · 2025Article
- Article
- Focal adhesion in the tumour metastasis: from molecular mechanisms to therapeutic targets.Biomarker research · 2025Review
- Comprehensive dissection of cis-regulatory elements in a 2.8 Mb topologically associated domain in six human cancers.Nature communications · 2025Article
- BET inhibitors (BETi) influence oxidative phosphorylation metabolism by affecting mitochondrial dynamics leading to alterations in apoptotic pathways in triple-negative breast cancer (TNBC) cells.Cell proliferation · 2024Article
- Synergistic effects of combined BET and FAK inhibition against Vestibular Schwannomas in NF2-related Schwannomatosis.Oncogene · 2024Article
- BRD4-specific PROTAC inhibits basal-like breast cancer partially through downregulating KLF5 expression.Oncogene · 2024Article
- Divergent Processing of Cell Stress Signals as the Basis of Cancer Progression: Licensing NFκB on Chromatin.International journal of molecular sciences · 2024Review
- MCL1 Inhibition Overcomes the Aggressiveness Features of Triple-Negative Breast Cancer MDA-MB-231 Cells.International journal of molecular sciences · 2023Article
- High Expression Level of BRD4 Is Associated with a Poor Prognosis and Immune Infiltration in Esophageal Squamous Cell Carcinoma.Digestive diseases and sciences · 2023Article
- Targeting regulated cell death (RCD) with small-molecule compounds in triple-negative breast cancer: a revisited perspective from molecular mechanisms to targeted therapies.Journal of hematology & oncology · 2022Review
- Review
- FGFR2-BRD4 Axis Regulates Transcriptional Networks of Histone 3 Modification and Synergy Between Its Inhibitors and PD-1/PD-L1 in a TNBC Mouse Model.Frontiers in immunology · 2022Article
- Article
Corrections and comments
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Authors and funding
25 authors at 6 institutions in 2 countries.
Funding
Abstract
purposeStemming from a myriad of genetic and epigenetic alterations, triple-negative breast cancer (TNBC) is tied to poor clinical outcomes and aspires for individualized therapies. Here we investigated the therapeutic potential of co-inhibiting integrin-dependent signaling pathway and BRD4, a transcriptional and epigenetic mediator, for TNBC.
methodsTwo independent patient cohorts were subjected to bioinformatic and IHC examination for clinical association of candidate cancer drivers. The efficacy and biological bases for co-targeting these drivers were interrogated using cancer cell lines, a protein kinase array, chemical inhibitors, RNAi/CRISPR/Cas9 approaches, and a 4 T1-Balb/c xenograft model.
resultsWe found that amplification of the chromosome 8q24 region occurred in nearly 20% of TNBC tumors, and that it coincided with co-upregulation or amplification of c-Myc and FAK, a key effector of integrin-dependent signaling. This co-upregulation at the mRNA or protein level correlated with a poor patient survival (p < 0.0109 or p < 0.0402, respectively). Furthermore, we found that 14 TNBC cell lines exhibited high vulnerabilities to the combination of JQ1 and VS-6063, potent pharmacological antagonists of the BRD4/c-Myc and integrin/FAK-dependent pathways, respectively. We also observed a cooperative inhibitory effect of JQ1 and VS-6063 on tumor growth and infiltration of Ly6G
conclusionBased on our results, we conclude that the BRD4/c-Myc- and integrin/FAK-dependent pathways act in concert to promote breast cancer cell survival and poor clinical outcomes. As such, they represent promising targets for a synthetic lethal-type of therapy against TNBC.
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Registered trials
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