ArticleNature communications2021
BAF complexes drive proliferation and block myogenic differentiation in fusion-positive rhabdomyosarcoma.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 56 citations in OpenAlex.
- The roles of chromatin remodeling and 3D genome organization in cancers: from mechanistic insights to emerging treatment options.Molecular cancer · 2026Review
- Selective sensitivity of Ph-like B-cell acute lymphoblastic leukemia to BRG1 inhibition identifies a therapeutic vulnerability.Leukemia · 2026Article
- CDK8 Inhibition Releases the Muscle Differentiation Block in Fusion-driven Alveolar Rhabdomyosarcoma.Cancer discovery · 2026Article
- Clinical Significance of Bromodomain-Containing Protein 9 in Colorectal Cancer.Annals of surgical oncology · 2026Article
- Fusion-positive rhabdomyosarcoma oncofusions share a common interactome.Nature communications · 2026Article
- A SWI/SNF-specific Ig-like domain, SWIFT, is a transcription factor binding platform.Science (New York, N.Y.) · 2026Article
- From bench to bedside: combining HDAC inhibitors with standard therapies in rhabdomyosarcoma treatment.Frontiers in cell and developmental biology · 2026Review
- Integrative analysis reveals synergistic regulation of Sp7 by BRD9 and Wnt/β-catenin signaling during osteogenic differentiation.Communications biology · 2025Article
- PRKG1 hinders myogenic differentiation and predicts response to AKT inhibitor ipatasertib in Rhabdomyosarcoma.Nature communications · 2025Article
- RUNX2 inhibition disrupts a PAX3::FOXO1-RUNX2 feed-forward loop and dismantles oncogenic gene programs in fusion-positive rhabdomyosarcoma.bioRxiv : the preprint server for biology · 2025Article
- Rhabdomyosarcoma fusion oncoprotein initially pioneers a neural signature in vivo.Cell reports · 2025Article
- Polybromo 1/vimentin axis dictates tumor grade, epithelial-mesenchymal transition, and metastasis in pancreatic cancer.The Journal of clinical investigation · 2025Article
- Ephrin-A5 or EphA7 stimulation is anti-proliferative for human rhabdomyosarcoma in vitro.Skeletal muscle · 2025Article
- The Role of PAX7 in Breast Cancer Prognosis and Its Mechanistic Involvement in the Wnt/β-Catenin Pathway.Journal of cellular and molecular medicine · 2025Article
- Myogenic IGFBP5 levels in rhabdomyosarcoma are nourished by mesenchymal stromal cells and regulate growth arrest and apoptosis.Cell communication and signaling : CCS · 2025Article
- Article
- Short circuit: Transcription factor addiction as a growing vulnerability in cancer.Current opinion in structural biology · 2024Review
- Entinostat as a combinatorial therapeutic for rhabdomyosarcoma.Scientific reports · 2024Article
- Biological and therapeutic insights from animal modeling of fusion-driven pediatric soft tissue sarcomas.Disease models & mechanisms · 2024Review
- Chromatin profiling and state predictions reveal insights into epigenetic regulation during early porcine development.Epigenetics & chromatin · 2024Article
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Authors and funding
21 authors at 6 institutions in 2 countries.
Funding
Abstract
Rhabdomyosarcoma (RMS) is a pediatric malignancy of skeletal muscle lineage. The aggressive alveolar subtype is characterized by t(2;13) or t(1;13) translocations encoding for PAX3- or PAX7-FOXO1 chimeric transcription factors, respectively, and are referred to as fusion positive RMS (FP-RMS). The fusion gene alters the myogenic program and maintains the proliferative state while blocking terminal differentiation. Here, we investigated the contributions of chromatin regulatory complexes to FP-RMS tumor maintenance. We define the mSWI/SNF functional repertoire in FP-RMS. We find that SMARCA4 (encoding BRG1) is overexpressed in this malignancy compared to skeletal muscle and is essential for cell proliferation. Proteomic studies suggest proximity between PAX3-FOXO1 and BAF complexes, which is further supported by genome-wide binding profiles revealing enhancer colocalization of BAF with core regulatory transcription factors. Further, mSWI/SNF complexes localize to sites of de novo histone acetylation. Phenotypically, interference with mSWI/SNF complex function induces transcriptional activation of the skeletal muscle differentiation program associated with MYCN enhancer invasion at myogenic target genes, which is recapitulated by BRG1 targeting compounds. We conclude that inhibition of BRG1 overcomes the differentiation blockade of FP-RMS cells and may provide a therapeutic strategy for this lethal childhood tumor.
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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.