Home > Publications database > Subversion of mRNA degradation pathways by EWSR1::FLI1 represents a therapeutic vulnerability in Ewing sarcoma. > print

001     302857
005     20250720021504.0
024 7 _ |a 10.1038/s41467-025-61725-x
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082 _ _ |a 500
100 1 _ |a Galvan, Bartimée
|0 0000-0001-8629-4860
|b 0
245 _ _ |a Subversion of mRNA degradation pathways by EWSR1::FLI1 represents a therapeutic vulnerability in Ewing sarcoma.
260 _ _ |a [London]
|c 2025
|b Springer Nature
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520 _ _ |a Many cancers are defined by gene fusions that frequently encode oncogenic transcription factors (TFs), such as EWSR1::FLI1 in Ewing sarcoma (EwS). Here, we report that independently to its canonical roles in transcription, EWSR1::FLI1 also functions as an mRNA decay factor, reshaping mRNA stability in EwS. This function participates in EWSR1::FLI1 tumorigenicity and involves interactions of EWSR1::FLI1 with the CCR4-NOT deadenylation complex via its EWSR1-derived low-complexity domain and with the RNA-binding protein HuR/ELAVL1 via its FLI1-derived region. Strikingly, we find that EWSR1::FLI1-mediated mRNA decay antagonizes the normal mRNA protective function of HuR and renders EwS cells highly sensitive to HuR inhibition. Our findings uncover a post-transcriptional function of EWSR1::FLI1 and suggest that targeting mRNA stability mechanisms may offer therapeutic opportunities for EwS.
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650 _ 7 |a Proto-Oncogene Protein c-fli-1
|2 NLM Chemicals
650 _ 7 |a EWSR1 protein, human
|2 NLM Chemicals
650 _ 7 |a RNA-Binding Protein EWS
|2 NLM Chemicals
650 _ 7 |a FLI1 protein, human
|2 NLM Chemicals
650 _ 7 |a Oncogene Proteins, Fusion
|2 NLM Chemicals
650 _ 7 |a RNA, Messenger
|2 NLM Chemicals
650 _ 7 |a RNA-Binding Proteins
|2 NLM Chemicals
650 _ 2 |a Sarcoma, Ewing: genetics
|2 MeSH
650 _ 2 |a Sarcoma, Ewing: metabolism
|2 MeSH
650 _ 2 |a Sarcoma, Ewing: pathology
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Proto-Oncogene Protein c-fli-1: metabolism
|2 MeSH
650 _ 2 |a Proto-Oncogene Protein c-fli-1: genetics
|2 MeSH
650 _ 2 |a RNA Stability: genetics
|2 MeSH
650 _ 2 |a RNA-Binding Protein EWS: metabolism
|2 MeSH
650 _ 2 |a RNA-Binding Protein EWS: genetics
|2 MeSH
650 _ 2 |a Cell Line, Tumor
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Oncogene Proteins, Fusion: metabolism
|2 MeSH
650 _ 2 |a Oncogene Proteins, Fusion: genetics
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a RNA, Messenger: metabolism
|2 MeSH
650 _ 2 |a RNA, Messenger: genetics
|2 MeSH
650 _ 2 |a RNA-Binding Proteins: metabolism
|2 MeSH
650 _ 2 |a RNA-Binding Proteins: genetics
|2 MeSH
650 _ 2 |a Gene Expression Regulation, Neoplastic
|2 MeSH
650 _ 2 |a Bone Neoplasms: genetics
|2 MeSH
650 _ 2 |a Bone Neoplasms: metabolism
|2 MeSH
700 1 _ |a Ongena, Loïc
|0 0000-0002-7768-1428
|b 1
700 1 _ |a Bruyr, Jonathan
|b 2
700 1 _ |a Fettweis, Gregory
|0 0000-0002-6623-2264
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700 1 _ |a Lucarelli, Eva
|b 4
700 1 _ |a Lavergne, Arnaud
|0 0000-0003-4817-3202
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700 1 _ |a Mariavelle, Emeline
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700 1 _ |a O'Grady, Tina M
|0 0000-0002-1283-0293
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700 1 _ |a Hassoun, Zahrat El Oula
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700 1 _ |a Claes, Margaux
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700 1 _ |a Dubois, Laurence
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700 1 _ |a Lee, Kevin A W
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700 1 _ |a Kruys, Véronique
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700 1 _ |a Gueydan, Cyril
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700 1 _ |a Durand, Jules
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700 1 _ |a Hervouet, Eric
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700 1 _ |a Geyer, Florian
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700 1 _ |a Mao, Lianghao
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700 1 _ |a Cidre-Aranaz, Florencia
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700 1 _ |a Twizere, Jean-Claude
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700 1 _ |a Dequiedt, Franck
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773 _ _ |a 10.1038/s41467-025-61725-x
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