2026-07-16T14:10:11Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/134992025-04-29T10:36:43Zcom_20.500.12105_14556com_20.500.12105_2337com_20.500.12105_2336com_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_14558col_20.500.12105_19616
Repisalud
author
Garcia-Garcia, Laura
author
Fernández-Tabanera, Enrique
author
Cervera Mayor, Saint Thomas
author
Melero-Fernández de Mera, Raquel María
author
Josa, Santiago
author
Gonzalez-Gonzalez, Laura
author
Rodriguez-Martin, Carlos
author
Grünewald, Thomas G P
author
Alonso, Javier
funder
Instituto de Salud Carlos III
funder
Asociación Pablo Ugarte contra el cáncer infantil
funder
Candela Ribera. Asociación contra el sarcoma de Ewing
funder
Asociación Todos somos Iván
funder
Fundación la Sonrisa de Alex para la investigación y el tratamiento del sarcoma de Ewing
funder
Centro de Investigación Biomedica en Red - CIBER
2021-12-20T13:36:14Z
2021-12-20T13:36:14Z
2021-11-12
Cancers (Basel). 2021 Nov 12;13(22):5668.
10.3390/cancers13225668
2072-6694
Cancers
34830820
http://hdl.handle.net/20.500.12105/13499
Ewing sarcoma is a rare pediatric tumor characterized by chromosomal translocations that give rise to aberrant chimeric transcription factors (e.g., EWSR1-FLI1). EWSR1-FLI1 promotes a specific cellular transcriptional program. Therefore, the study of EWSR1-FLI1 target genes is important to identify critical pathways involved in Ewing sarcoma tumorigenesis. In this work, we focused on the transcription factors regulated by EWSR1-FLI1 in Ewing sarcoma. Transcriptomic analysis of the Ewing sarcoma cell line A673 indicated that one of the genes more strongly upregulated by EWSR1-FLI1 was FEZF1 (FEZ family zinc finger protein 1), a transcriptional repressor involved in neural cell identity. The functional characterization of FEZF1 was performed in three Ewing sarcoma cell lines (A673, SK-N-MC, SK-ES-1) through an shRNA-directed silencing approach. FEZF1 knockdown inhibited clonogenicity and cell proliferation. Finally, the analysis of the FEZF1-dependent expression profile in A673 cells showed several neural genes regulated by FEZF1 and concomitantly regulated by EWSR1-FLI1. In summary, FEZF1 is transcriptionally regulated by EWSR1-FLI1 in Ewing sarcoma cells and is involved in the regulation of neural-specific genes, which could explain the neural-like phenotype observed in several Ewing sarcoma tumors and cell lines.
eng
EWSR1-FLI1
Ewing sarcoma
FEZF11
GGAA-microsatellites
The Transcription Factor FEZF1, a Direct Target of EWSR1-FLI1 in Ewing Sarcoma Cells, Regulates the Expression of Neural-Specific Genes
research article
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