ArticleGenes & cancer2015
EWS/FLI utilizes NKX2-2 to repress mesenchymal features of Ewing sarcoma.
Article in Genes & cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 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
32 citing papers in PubMed, 45 citations in OpenAlex.
- STAG2 loss amplifies EWS-FLI1-driven microsatellite enhancer activity promoting Ewing sarcoma aggressiveness.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Tissue-Specific Expression of the EWSR1::FLI1 Fusion Protein IdentifiesInternational journal of molecular sciences · 2026Article
- Article
- Autocrine TGFβ2 enforces a transcriptionally hybrid cell state in Ewing sarcoma.Science advances · 2026Article
- Autocrine TGFβ2 enforces a transcriptionally hybrid cell state in Ewing sarcoma.bioRxiv : the preprint server for biology · 2025Article
- Preclinical models for the study of pediatric solid tumors: focus on bone sarcomas.Frontiers in oncology · 2024Review
- Cancer-Associated Fibroblast-Like Tumor Cells Remodel the Ewing Sarcoma Tumor Microenvironment.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- EWS/FLI1 Characterization, Activation, Repression, Target Genes and Therapeutic Opportunities in Ewing Sarcoma.International journal of molecular sciences · 2023Review
- CRISPR-Cas9 knockout screening identifies KIAA1429 as an essential gene in Ewing sarcoma.Journal of experimental & clinical cancer research : CR · 2023Article
- Carcinoma-associated fibroblast-like tumor cells remodel the Ewing sarcoma tumor microenvironment.bioRxiv : the preprint server for biology · 2023Article
- The ETS transcription factor ETV6 constrains the transcriptional activity of EWS-FLI to promote Ewing sarcoma.Nature cell biology · 2023Article
- Systematic multi-omics cell line profiling uncovers principles of Ewing sarcoma fusion oncogene-mediated gene regulation.Cell reports · 2022Article
- TrkC, a novel prognostic marker, induces and maintains cell survival and metastatic dissemination of Ewing sarcoma by inhibiting EWSR1-FLI1 degradation.Cell death & disease · 2022Article
- Epigenetic and Transcriptional Signaling in Ewing Sarcoma-Disease Etiology and Therapeutic Opportunities.Biomedicines · 2022Review
- AT-hook DNA-binding motif-containing protein one knockdown downregulates EWS-FLI1 transcriptional activity in Ewing's sarcoma cells.PloS one · 2022Article
- Construction of a Prognosis-Related Gene Signature by Weighted Gene Coexpression Network Analysis in Ewing Sarcoma.Computational and mathematical methods in medicine · 2022Article
- The importance of fusion protein activity in Ewing sarcoma and the cell intrinsic and extrinsic factors that regulate it: A review.Frontiers in oncology · 2022Review
- The Transcription FactorCancers · 2021Article
- Article
- EWS-FLI1 regulates and cooperates with core regulatory circuitry in Ewing sarcoma.Nucleic acids research · 2020Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
In Ewing sarcoma, NKX2-2 is a critical activated target of the oncogenic transcription factor EWS/FLI that is required for transformation. However, its biological function in this malignancy is unknown. Here we provide evidence that NKX2-2 mediates the EWS/FLI-controlled block of mesenchymal features. Transcriptome-wide RNA sequencing revealed that NKX2-2 represses cell adhesion and extracellular matrix organization genes. NKX2-2-depleted cells form more focal adhesions and organized actin stress fibers, and spread over a wider area-hallmarks of mesenchymally derived cells. Furthermore, NKX2-2 represses the actin-stabilizing protein zyxin, suggesting that these morphological changes are attributable to zyxin de-repression. In addition, NKX2-2-knockdown cells display marked increases in migration and substrate adhesion. However, only part of the EWS/FLI phenotype is NKX2-2-dependent; consequently, NKX2-2 is insufficient to rescue EWS/FLI repression of mesenchymalization. Strikingly, we found that EWS/FLI-and NKX22-repressed genes are activated by ZEB2, which was previously shown to block Ewing sarcoma epithelialization. Together, these data support an emerging theme wherein Ewing sarcoma cells highly express transcription factors that maintain an undifferentiated state. Importantly, co-opting epithelial and mesenchymal traits by Ewing sarcoma cells may explain how the primary tumor grows rapidly while also "passively" metastasizing, without the need for transitions toward differentiated states, as in carcinomas.
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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.