ArticleCancer discovery2023
p53 Gain-of-Function Mutation Induces Metastasis via BRD4-Dependent CSF-1 Expression.
Article in Cancer discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
34 citing papers in PubMed, 42 citations in OpenAlex.
- Mutant TP53 hijacks RNA-splicing factor RBM28 to suppress double-stranded RNA triggered antitumor immunity.Nature communications · 2026Article
- LFPM inhibition of RING1-mediated p53Cell death and differentiation · 2026Article
- Genomic Enrichment and Functional Impact of TP53 and CYLD Alterations in Recurrent and Metastatic HPV-Associated Head and Neck Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- The impact of p53 mutation on tumor immune evasion: mechanistic insights and clinical implications.Frontiers in immunology · 2026Review
- Preclinical evaluation of JQ1 in esophageal squamous cell carcinoma: growth and migration suppression with BRD4-associated DNA damage and apoptotic signaling.Frontiers in pharmacology · 2026Article
- Integrative single-cell and genomic analysis reveals NMB as a driver of metastatic adaptation in esophageal squamous cell carcinoma via metabolic rewiring and immune evasion.Frontiers in cell and developmental biology · 2026Article
- Association of macrophage colony-stimulating factor 1 and its locus with osteoarthritis: Mendelian randomization and colocalization analysis.Clinical rheumatology · 2025Article
- Mutant p53 regulates cancer cell invasion in complex three-dimensional environments through mevalonate pathway-dependent Rho/ROCK signaling.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- BRD9-p53-E2F1 circuit orchestrates cell growth and DNA damage repair in gastric cancer.Molecular cancer · 2025Article
- P53 Function Status Correlates With Overall Survival in Patients With Resected Pancreatic Cancer.Journal of surgical oncology · 2025Article
- Multiple roles of p53 in cancer development: Regulation of tumor microenvironment, mJournal of advanced research · 2025Review
- Copy number amplification of TTPAL promotes cholesterol biosynthesis and esophageal squamous cell carcinoma progression via elevating NSUN2-mediated m5C modification of SREBP2 mRNA.Journal of experimental & clinical cancer research : CR · 2025Article
- NFIC suppressed the epithelial ovarian cancer via modulating the balance of PTEN/TGFβ1/EGR1/BRD4 and SP1/EZH2 induced Inhibition of TBX2/MMPs signaling.Scientific reports · 2025Article
- Article
- Lung-specific metastasis: the coevolution of tumor cells and lung microenvironment.Molecular cancer · 2025Review
- Squamous cell cancers of the aero-upper digestive tract: A unified perspective on biology, genetics, and therapy.Cancer cell · 2025Review
- Tp53 determines the spatial dynamics of M1/M2 tumor-associated macrophages and M1-driven tumoricidal effects.Cell death & disease · 2025Article
- Parthenolide improves sepsis-induced coagulopathy by inhibiting mitochondrial-mediated apoptosis in vascular endothelial cells through BRD4/BCL-xL pathway.Journal of translational medicine · 2025Article
- Article
- Exploring the Impact of miR-34b-5p on BRD4 Gene Expression in Triple-Negative Breast Cancer Cells.BioMed research international · 2025Article
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 1 country.
Funding
Abstract
TP53 mutations are frequent in esophageal squamous cell carcinoma (ESCC) and other SCCs and are associated with a proclivity for metastasis. Here, we report that colony-stimulating factor-1 (CSF-1) expression is upregulated significantly in a p53-R172H-dependent manner in metastatic lung lesions of ESCC. The p53-R172H-dependent CSF-1 signaling, through its cognate receptor CSF-1R, increases tumor cell invasion and lung metastasis, which in turn is mediated in part through Stat3 phosphorylation and epithelial-to-mesenchymal transition (EMT). In Trp53R172H tumor cells, p53 occupies the Csf-1 promoter. The Csf-1 locus is enriched with histone 3 lysine 27 acetylation (H3K27ac), which is likely permissive for fostering an interaction between bromodomain-containing domain 4 (BRD4) and p53-R172H to regulate Csf-1 transcription. Inhibition of BRD4 not only reduces tumor invasion and lung metastasis but also reduces circulating CSF-1 levels. Overall, our results establish a novel p53-R172H-dependent BRD4-CSF-1 axis that promotes ESCC lung metastasis and suggest avenues for therapeutic strategies for this difficult-to-treat disease. SIGNIFICANCE: The invasion-metastasis cascade is a recalcitrant barrier to effective cancer therapy. We establish that the p53-R172H-dependent BRD4-CSF-1 axis is a mediator of prometastatic properties, correlates with patient survival and tumor stages, and its inhibition significantly reduces tumor cell invasion and lung metastasis. This axis can be exploited for therapeutic advantage. This article is featured in Selected Articles from This Issue, p. 2489.
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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.