期刊
CANCER LETTERS
卷 323, 期 2, 页码 208-214出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2012.04.012
关键词
Cathepsin D; Apoptosis; Autophagy; DNA-PK; Oxidative stress
类别
资金
- clinical research grant from Gyeongsang National University Hospital
- Basic Science Research Program through the National Research Foundation of Korea (NRF)
- Ministry of Education Science and Technology [NRF-2009-0071600, 2012-0000305]
Cathepsin D (CatD), a lysosomal aspartic protease, plays an essential role in tumor progression and apoptosis. However, the function of CatD in cell death is not yet fully understood. In this study, we identified CatD as one of up-regulated proteins in human malignant glioblastoma M059J cells that lack the catalytic subunit of DNA-PK compared with its isogenic M059K cells with normal DNA-PK activity. M059J cells were relatively more resistant to genotoxic stress than M059K cells. Overexpression of wild-type CatD but not catalytically inactive mutant CatD (D295N) inhibited H2O2-induced cell death in HeLa cells. Furthermore, knockdown of CatD expression abolished anti-apoptotic effect by CatD in the presence of H2O2. Interestingly, high expression of CatD in HeLa cells significantly activated autophagy: increase of acidic autophagic vacuoles, LC3-II formation, and GFP-LC3 puncta. These results suggest that CatD can function as an anti-apoptotic mediator by inducing autophagy under cellular stress. In conclusion, inhibition of autophagy could be a novel strategy for the adjuvant chemotherapy of CatD-expressing cancers. (c) 2012 Elsevier Ireland Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据