ArticlePLoS genetics2020
The PAX-FOXO1s trigger fast trans-differentiation of chick embryonic neural cells into alveolar rhabdomyosarcoma with tissue invasive properties limited by S phase entry inhibition.
Article in PLoS genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 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
14 citing papers in PubMed, 17 citations in OpenAlex.
- System for study of diverse cellular composition in alveolar rhabdomyosarcoma.Scientific reports · 2026Article
- PAX3: A Driver of Normal Development and Disease.Biomolecules · 2026Review
- Review
- Dual transcriptional activities of PAX3 and PAX7 spatially encode spinal cell fates through distinct gene networks.PLoS biology · 2025Article
- Rhabdomyosarcoma fusion oncoprotein initially pioneers a neural signature in vivo.Cell reports · 2025Article
- Fusion oncogenes in rhabdomyosarcoma: model systems, mechanisms of tumorigenesis, and therapeutic implications.Frontiers in oncology · 2025Review
- Biological and therapeutic insights from animal modeling of fusion-driven pediatric soft tissue sarcomas.Disease models & mechanisms · 2024Review
- Myogenesis gone awry: the role of developmental pathways in rhabdomyosarcoma.Frontiers in cell and developmental biology · 2024Review
- PAX3-FOXO1 dictates myogenic reprogramming and rhabdomyosarcoma identity in endothelial progenitors.Nature communications · 2023Article
- A Review of the Regulatory Mechanisms of N-Myc on Cell Cycle.Molecules (Basel, Switzerland) · 2023Review
- Single-cell analysis and functional characterization uncover the stem cell hierarchies and developmental origins of rhabdomyosarcoma.Nature cancer · 2022Article
- Review
- Complex Elucidation of Cells-of-Origin in Pediatric Soft Tissue Sarcoma: From Concepts to Real Life, Hide-and-Seek through Epigenetic and Transcriptional Reprogramming.International journal of molecular sciences · 2022Review
- Divergent transcriptional and transforming properties of PAX3-FOXO1 and PAX7-FOXO1 paralogs.PLoS genetics · 2022Article
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 2 countries.
Funding
Abstract
The chromosome translocations generating PAX3-FOXO1 and PAX7-FOXO1 chimeric proteins are the primary hallmarks of the paediatric fusion-positive alveolar subtype of Rhabdomyosarcoma (FP-RMS). Despite the ability of these transcription factors to remodel chromatin landscapes and promote the expression of tumour driver genes, they only inefficiently promote malignant transformation in vivo. The reason for this is unclear. To address this, we developed an in ovo model to follow the response of spinal cord progenitors to PAX-FOXO1s. Our data demonstrate that PAX-FOXO1s, but not wild-type PAX3 or PAX7, trigger the trans-differentiation of neural cells into FP-RMS-like cells with myogenic characteristics. In parallel, PAX-FOXO1s remodel the neural pseudo-stratified epithelium into a cohesive mesenchyme capable of tissue invasion. Surprisingly, expression of PAX-FOXO1s, similar to wild-type PAX3/7, reduce the levels of CDK-CYCLIN activity and increase the fraction of cells in G1. Introduction of CYCLIN D1 or MYCN overcomes this PAX-FOXO1-mediated cell cycle inhibition and promotes tumour growth. Together, our findings reveal a mechanism that can explain the apparent limited oncogenicity of PAX-FOXO1 fusion transcription factors. They are also consistent with certain clinical reports indicative of a neural origin of FP-RMS.
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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.