ArticleNature communications2023
SIX1 and EWS/FLI1 co-regulate an anti-metastatic gene network in Ewing Sarcoma.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
8 citing papers in PubMed, 11 citations in OpenAlex.
- Six1 haploinsufficiency is associated with activation of NF-κB and TNF-related transcriptional signatures in aging mice.Cell death & disease · 2026Article
- Multimodal bioinformatic analyses of genome-scale expression beyond gene-centric differential expression.Briefings in bioinformatics · 2026Review
- Integrins identified as potential prognostic markers in osteosarcoma through multi-omics and multi-dataset analysis.NPJ precision oncology · 2025Article
- ETS-1 in tumor immunology: implications for novel anti-cancer strategies.Frontiers in immunology · 2025Review
- Integrative analysis of T cell-associated markers in Ewing sarcoma reveals prognostic signatures and immune dynamics.Frontiers in immunology · 2025Article
- Implications of ITCH-mediated ubiquitination of SIX1 on CDC27-cyclinB1 signaling in nasopharyngeal carcinoma.Scientific reports · 2024Article
- Article
- Advances in ex vivo expansion of hematopoietic stem and progenitor cells for clinical applications.Frontiers in bioengineering and biotechnology · 2024Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
Ewing sarcoma (ES), which is characterized by the presence of oncogenic fusion proteins such as EWS/FLI1, is an aggressive pediatric malignancy with a high rate of early dissemination and poor outcome after distant spread. Here we demonstrate that the SIX1 homeoprotein, which enhances metastasis in most tumor types, suppresses ES metastasis by co-regulating EWS/FLI1 target genes. Like EWS/FLI1, SIX1 promotes cell growth/transformation, yet dramatically inhibits migration and invasion, as well as metastasis in vivo. We show that EWS/FLI1 promotes SIX1 protein expression, and that the two proteins share genome-wide binding profiles and transcriptional regulatory targets, including many metastasis-associated genes such as integrins, which they co-regulate. We further show that SIX1 downregulation of integrins is critical to its ability to inhibit invasion, a key characteristic of metastatic cells. These data demonstrate an unexpected anti-metastatic function for SIX1, through coordinate gene regulation with the key oncoprotein in ES, EWS/FLI1.
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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.