ArticleProceedings of the National Academy of Sciences of the United States of America2021
Brd4-bound enhancers drive cell-intrinsic sex differences in glioblastoma.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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Who cites it
29 citing papers in PubMed, 46 citations in OpenAlex.
- Patient-derived glioblastoma cultures preserve respiration phenotypes during ex vivo maintenance and show sex-associated differences in migration.Acta neuropathologica communications · 2026Article
- Targeting BRD4-A Promising Therapeutic Option for Glioblastoma?International journal of molecular sciences · 2026Review
- Advancements in Drug Delivery Systems in Glioblastoma Therapy.International journal of molecular sciences · 2026Review
- NF-κB and STAT3 signaling uniquely stratify survival in female glioblastoma patients.iScience · 2026Article
- Gender and sex interactions are intrinsic components of cancer phenotypes.Nature reviews. Cancer · 2025Review
- TMBIM6 promotes glioma progression according to integrated bioinformatics and experimental evidence.Scientific reports · 2025Article
- Immunometabolic landscape of glioblastoma - a comparative analysis of circulating cytokines and biochemical markers.Contemporary oncology (Poznan, Poland) · 2025Article
- Annotation of cis-regulatory-associated histone modifications in the genomes of two Thoroughbred stallions.Frontiers in genetics · 2025Article
- Epigenetic developmental mechanisms underlying sex differences in cancer.The Journal of clinical investigation · 2024Review
- Deletion of Pax1 scoliosis-associated regulatory elements leads to a female-biased tail abnormality.Cell reports · 2024Article
- Pycallingcards: an integrated environment for visualizing, analyzing, and interpreting Calling Cards data.Bioinformatics (Oxford, England) · 2024Article
- Early growth response 1 transcription factor and its context-dependent functions in glioblastoma.Contemporary oncology (Poznan, Poland) · 2024Review
- Methylation of BRD4 by PRMT1 regulates BRD4 phosphorylation and promotes ovarian cancer invasion.Cell death & disease · 2023Article
- Calling Cards: A Customizable Platform to Longitudinally Record Protein-DNA Interactions Over Time in Cells and Tissues.Current protocols · 2023Article
- Calling Cards: a customizable platform to longitudinally record protein-DNA interactions over time in cells and tissues.bioRxiv : the preprint server for biology · 2023Article
- Article
- Superenhancers as master gene regulators and novel therapeutic targets in brain tumors.Experimental & molecular medicine · 2023Review
- Comprehensive analysis of the prognosis and immune infiltrates for the BET protein family reveals the significance of BRD4 in glioblastoma multiforme.Frontiers in cell and developmental biology · 2023Article
- Sex differences in brain tumor glutamine metabolism reveal sex-specific vulnerabilities to treatment.Med (New York, N.Y.) · 2022Article
- Measuring transcription factor binding and gene expression using barcoded self-reporting transposon calling cards and transcriptomes.NAR genomics and bioinformatics · 2022Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Sex can be an important determinant of cancer phenotype, and exploring sex-biased tumor biology holds promise for identifying novel therapeutic targets and new approaches to cancer treatment. In an established isogenic murine model of glioblastoma (GBM), we discovered correlated transcriptome-wide sex differences in gene expression, H3K27ac marks, large Brd4-bound enhancer usage, and Brd4 localization to Myc and p53 genomic binding sites. These sex-biased gene expression patterns were also evident in human glioblastoma stem cells (GSCs). These observations led us to hypothesize that Brd4-bound enhancers might underlie sex differences in stem cell function and tumorigenicity in GBM. We found that male and female GBM cells exhibited sex-specific responses to pharmacological or genetic inhibition of Brd4. Brd4 knockdown or pharmacologic inhibition decreased male GBM cell clonogenicity and in vivo tumorigenesis while increasing both in female GBM cells. These results were validated in male and female patient-derived GBM cell lines. Furthermore, analysis of the Cancer Therapeutic Response Portal of human GBM samples segregated by sex revealed that male GBM cells are significantly more sensitive to BET (bromodomain and extraterminal) inhibitors than are female cells. Thus, Brd4 activity is revealed to drive sex differences in stem cell and tumorigenic phenotypes, which can be abrogated by sex-specific responses to BET inhibition. This has important implications for the clinical evaluation and use of BET inhibitors.
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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.