Autophagy inhibition can overcome radioresistance in breast cancer cells through suppression of TAK1 activation

Title
Autophagy inhibition can overcome radioresistance in breast cancer cells through suppression of TAK1 activation
Authors
MYUNG WOUL HANJONG CHEOL LEEJUN-YOUNG CHOIGUI CHUL KIMHYO WON CHANGHAE YUN NAMSEONG WHO KIM김상윤
Keywords
Autophagy; TAK1; breast cancer; radioresistance
Issue Date
2014-03
Publisher
Anticancer research
Citation
VOL 34, NO 3, 1449-1455
Abstract
Background/Aim: Autophagy is frequently activated in radioresistant cancer cells. In the present study, we evaluated the role of autophagy and transforming growth factor-activated kinase 1 (TAK1) in radioresistance. Materials and Methods: TAK1 phosphorylation in MDA-MB231 breast cancer cells was evaluated by western blotting. The regulatory effects of the TAK1 inhibitor and autophagy inhibitor were assessed by cell morphology, cell survival and induction of apoptosis. Results: Radiation induced the phosphorylation of TAK1, whereas the inhibition of TAK1 activity enhanced the cytotoxicity of radiation in MDA-MB231 cells. Autophagy inhibitors significantly enhanced radiation-induced apoptosis of MDA-MB231 cells. This augmentation in radiosensitivity seemed to result from the suppression of TAK1 activation. Conclusion: Inhibition of autophagy enhanced radiosensitivity through suppression of radiation-induced TAK1 activation, suggesting that the modulation of TAK1-induced autophagy may be a good therapeutic strategy to treat radioresistant breast cancer.
URI
http://pubs.kist.re.kr/handle/201004/48679
ISSN
02507005
Appears in Collections:
KIST Publication > Article
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