Inhibition of Karyopherin-α2 Augments Radiation-Induced Cell Death by Perturbing BRCA1-Mediated DNA Repair.
Int J Mol Sci
; 20(11)2019 Jun 11.
Article
en En
| MEDLINE
| ID: mdl-31212646
ABSTRACT
Ionizing radiation (IR) has been widely used in the treatment of cancer. Radiation-induced DNA damage triggers the DNA damage response (DDR), which can confer radioresistance and early local recurrence by activating DNA repair pathways. Since karyopherin-α2 (KPNA2), playing an important role in nucleocytoplasmic transport, was significantly increased by IR in our previous study, we aimed to determine the function of KPNA2 with regard to DDR. Exposure to radiation upregulated KPNA2 expression in human colorectal cancer HT29 and HCT116 cells and breast carcinoma MDA-MB-231 cells together with the increased expression of DNA repair protein BRCA1. The knockdown of KPNA2 effectively increased apoptotic cell death via inhibition of BRCA1 nuclear import following IR. Therefore, we propose that KPNA2 is a potential target for overcoming radioresistance via interruption to DDR.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Supervivencia Celular
/
Muerte Celular
/
Proteína BRCA1
/
Alfa Carioferinas
Límite:
Humans
Idioma:
En
Año:
2019
Tipo del documento:
Article