Elevated CXorf67 Expression in PFA Ependymomas Suppresses DNA Repair and Sensitizes to PARP Inhibitors.
Cancer Cell
; 38(6): 844-856.e7, 2020 12 14.
Article
em En
| MEDLINE
| ID: mdl-33186520
ABSTRACT
Ependymoma is the third most common pediatric tumor with posterior fossa group A (PFA) being its most aggressive subtype. Ependymomas are generally refractory to chemotherapies and thus lack any effective treatment. Here, we report that elevated expression of CXorf67 (chromosome X open reading frame 67), which frequently occurs in PFA ependymomas, suppresses homologous recombination (HR)-mediated DNA repair. Mechanistically, CXorf67 interacts with PALB2 and inhibits PALB2-BRCA2 interaction, thereby inhibiting HR repair. Concordantly, tumor cells with high CXorf67 expression levels show increased sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors, especially when combined with radiotherapy. Thus, our findings have revealed a role of CXorf67 in HR repair and suggest that combination of PARP inhibitors with radiotherapy could be an effective treatment option for PFA ependymomas.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Infratentoriais
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Proteínas Oncogênicas
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Proteína BRCA2
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Ependimoma
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Inibidores de Poli(ADP-Ribose) Polimerases
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Proteína do Grupo de Complementação N da Anemia de Fanconi
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article