2026-06-14T03:44:39Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/133212025-04-29T10:35:40Zcom_20.500.12105_14556com_20.500.12105_2337com_20.500.12105_2336com_20.500.12105_2052com_20.500.12105_2051com_20.500.12105_15322col_20.500.12105_14558col_20.500.12105_19616col_20.500.12105_16988
Repisalud
author
Cervera Mayor, Saint Thomas
author
Rodriguez-Martin, Carlos
author
Fernández-Tabanera, Enrique
author
Melero-Fernández de Mera, Raquel María
author
Morin, Matias
author
Fernández-Peñalver, Sergio
author
Iranzo-Martínez, Maria
author
Amhih-Cardenas, Jorge
author
Garcia-Garcia, Laura
author
Gonzalez-Gonzalez, Laura
author
Moreno-Pelayo, Miguel Angel
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
Fundación la Sonrisa de Alex para la investigación y el tratamiento del sarcoma de Ewing
funder
Centro de Investigación Biomedica en Red - CIBER
funder
Comunidad de Madrid (España)
funder
Asociación Todos somos Iván
2021-08-26T19:01:45Z
2021-08-26T19:01:45Z
2021-07-27
Cancers (Basel) . 2021;13(15):3783.
10.3390/cancers13153783
2072-6694
Cancers
34359682
http://hdl.handle.net/20.500.12105/13321
Ewing sarcoma is an aggressive bone cancer affecting children and young adults. The main molecular hallmark of Ewing sarcoma are chromosomal translocations that produce chimeric oncogenic transcription factors, the most frequent of which is the aberrant transcription factor EWSR1-FLI1. Because this is the principal oncogenic driver of Ewing sarcoma, its inactivation should be the best therapeutic strategy to block tumor growth. In this study, we genetically inactivated EWSR1-FLI1 using CRISPR-Cas9 technology in order to cause permanent gene inactivation. We found that gene editing at the exon 9 of FLI1 was able to block cell proliferation drastically and induce senescence massively in the well-studied Ewing sarcoma cell line A673. In comparison with an extensively used cellular model of EWSR1-FLI1 knockdown (A673/TR/shEF), genetic inactivation was more effective, particularly in its capability to block cell proliferation. In summary, genetic inactivation of EWSR1-FLI1 in A673 Ewing sarcoma cells blocks cell proliferation and induces a senescence phenotype that could be exploited therapeutically. Although efficient and specific in vivo CRISPR-Cas9 editing still presents many challenges today, our data suggest that complete inactivation of EWSR1-FLI1 at the cell level should be considered a therapeutic approach to develop in the future.
eng
CRISPR/Cas9
EWSR1–FLI1
Ewing sarcoma
Cell cycle arrest
Gene therapy.
Senescence
Therapeutic Potential of EWSR1-FLI1 Inactivation by CRISPR/Cas9 in Ewing Sarcoma
research article
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