ArticleProceedings of the National Academy of Sciences of the United States of America2024
SP1 undergoes phase separation and activates RGS20 expression through super-enhancers to promote lung adenocarcinoma progression.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- ACAT1-Mediated SP1-K694 Lactylation Promotes M1 Macrophage Polarization via TREM1 Transcription in COPD.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- G-Quadruplexes: Structural Diversity and Emerging Roles in Biomolecular Condensation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Frequency-Domain Transformation of cfDNA End-Motif Profiles Enhances Robust Cancer Detection.Genes · 2026Article
- Epigenetically controlled endothelial promyelocytic leukemia drives liver inflammation and fibrosis.The Journal of clinical investigation · 2026Article
- Understanding super enhancers in genome architecture and their roles in livestock breeding.BMC genomics · 2026Review
- EBF3 suppresses lung adenocarcinoma progression and immune evasion via transcriptional repression of CCL24.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Mitochondrial DNA methylation predicts immunotherapy response and prognosis in lung adenocarcinoma: evidence from scRNA-Seq and machine learning.BMC cancer · 2026Article
- Targeting biomolecular condensates: beyond dissolution.BMC biology · 2026Review
- Overexpression and prognostic value of aspartate β-hydroxylase in lung adenocarcinoma: a comprehensive study based on bioinformatics and clinical tissue sample validation.World journal of surgical oncology · 2026Article
- Inflammation-induced LncRNA SNHG1 orchestrates spermatogonium development in non-obstructive azoospermia via IL-17 A signaling pathway.Cellular and molecular life sciences : CMLS · 2026Article
- Super-enhancer-driven core transcription factor FOXP1 delays endothelial cell senescence via phase separation-mediated SESN3 activation.Theranostics · 2026Article
- Anti-tumor effects and mechanism of the histone demethylase inhibitor GSK-J4 in non-small cell lung cancer cells.Medical oncology (Northwood, London, England) · 2025Article
- The SP1-SuperEnhancer-SPHK1 Axis Mediates Niraparib Resistance in TNBC.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Biomolecular condensates in lung cancer: from molecular mechanisms to therapeutic targeting.Cell death discovery · 2025Review
- Function ofOncology letters · 2025Review
- G-quadruplex-dependent transcriptional regulation by molecular condensation in the Bcl3 promoter.Nucleic acids research · 2025Article
- Biomolecular phase separation in tumorigenesis: from aberrant condensates to therapeutic vulnerabilities.Molecular cancer · 2025Review
- Transcription factor SP1 drives the malignant progression of oral squamous cell carcinoma and M2 macrophage polarization through transcription activation-mediated upregulation CLEC7A.Cytotechnology · 2025Article
- HighCancers · 2025Article
- Selective phase separation of transcription factors is driven by orthogonal molecular grammar.Nature communications · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
13 authors.
Funding
Abstract
Lung adenocarcinoma (LUAD) is the leading cause of cancer-related death worldwide, but the underlying molecular mechanisms remain largely unclear. The transcription factor (TF) specificity protein 1 (SP1) plays a crucial role in the development of various cancers, including LUAD. Recent studies have indicated that master TFs may form phase-separated macromolecular condensates to promote super-enhancer (SE) assembly and oncogene expression. In this study, we demonstrated that SP1 undergoes phase separation and that its zinc finger 3 in the DNA-binding domain is essential for this process. Through Cleavage Under Targets & Release Using Nuclease (CUT&RUN) using antibodies against SP1 and H3K27ac, we found a significant correlation between SP1 enrichment and SE elements, identified the regulator of the G protein signaling 20 (RGS20) gene as the most likely target regulated by SP1 through SE mechanisms, and verified this finding using different approaches. The oncogenic activity of SP1 relies on its phase separation ability and RGS20 gene activation, which can be abolished by glycogen synthase kinase J4 (GSK-J4), a demethylase inhibitor. Together, our findings provide evidence that SP1 regulates its target oncogene expression through phase separation and SE mechanisms, thereby promoting LUAD cell progression. This study also revealed an innovative target for LUAD therapies through intervening in SP1-mediated SE formation.
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