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Targeting the centriolar replication factor STIL synergizes with DNA damaging agents for treatment of ovarian cancer

Opened Access Targeting the centriolar replication factor STIL synergizes with DNA damaging agents for treatment of ovarian cancer

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Autor: Checa Rodríguez, Cintia
Rabinowicz, Noa
Mangala, Lingegowda S.
Brown, Kevin R.
Castiel, Asher
Fecha: 2017
Publicado en: Oncotarget, 8 (16), 27380-27392.
Tipo de documento: Artículo
Resumen: Advanced ovarian cancer is an incurable disease. Thus, novel therapies are required. We wished to identify new therapeutic targets for ovarian cancer. ShRNA screen performed in 42 ovarian cancer cell lines identified the centriolar replication factor STIL as an essential gene for ovarian cancer cells. This was verified in-vivo in orthotopic human ovarian cancer mouse models. STIL depletion by administration of siRNA in neutral liposomes resulted in robust anti-tumor effect that was further enhanced in combination with cisplatin. Consistent with this finding, STIL depletion enhanced the extent of DNA double strand breaks caused by DNA damaging agents. This was associated with centrosomal depletion, ongoing genomic instability and enhanced formation of micronuclei. Interestingly, the ongoing DNA damage was not associated with reduced DNA repair. Indeed, we observed that depletion of STIL enhanced canonical homologous recombination repair and increased BRCA1 and RAD51 foci in response to...
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Cita: Checa Rodríguez, C., Rabinowicz, N., Mangala, L.S., Brown, .R. y Castiel, A. (2017). Targeting the centriolar replication factor STIL synergizes with DNA damaging agents for treatment of ovarian cancer. Oncotarget, 8 (16), 27380-27392.
Tamaño: 5.150Mb
Formato: PDF

URI: http://hdl.handle.net/11441/63952

DOI: 10.18632/oncotarget.16068

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