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Inhibition of Karyopherin-α2 Augments Radiation-Induced Cell Death by Perturbing BRCA1-Mediated DNA Repair.

Authors :
Song, Kyung-Hee
Jung, Seung-Youn
Park, Jeong-In
Ahn, Jiyeon
Park, Jong Kuk
Um, Hong-Duck
Park, In-Chul
Hwang, Sang-Gu
Ha, Hunjoo
Song, Jie-Young
Source :
International Journal of Molecular Sciences; Jun2019, Vol. 20 Issue 11, p2843, 1p
Publication Year :
2019

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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
16616596
Volume :
20
Issue :
11
Database :
Complementary Index
Journal :
International Journal of Molecular Sciences
Publication Type :
Academic Journal
Accession number :
137037200
Full Text :
https://doi.org/10.3390/ijms20112843