Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/13321
Título
Therapeutic Potential of EWSR1-FLI1 Inactivation by CRISPR/Cas9 in Ewing Sarcoma.
Autor(es)
Cervera Mayor, Saint Thomas ISCIII | Rodriguez-Martin, Carlos ISCIII | Fernández-Tabanera, Enrique ISCIII | Melero-Fernández de Mera, Raquel M ISCIII | Morin, Matias | Fernández-Peñalver, Sergio | Iranzo-Martínez, Maria ISCIII | Amhih-Cardenas, Jorge | Garcia-Garcia, Laura ISCIII | Gonzalez-Gonzalez, Laura ISCIII | Moreno-Pelayo, Miguel Angel | Alonso, Javier ISCIII
Fecha de publicación
2021-07-27
Cita
Cancers (Basel) . 2021;13(15):3783.
Idioma
Inglés
Tipo de documento
journal article
Resumen
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.
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