Mitophagy promotes replication of oncolytic Newcastle disease virus by blocking intrinsic apoptosis in lung cancer cells

文献类型: 外文期刊

第一作者: Meng, Gang

作者: Meng, Gang;Xia, Mao;Wang, Diancheng;Chen, Aiping;Wang, Hongwei;Yu, Decai;Wei, Jiwu;Yu, Decai;Wei, Jiwu;Wang, Yongshan

作者机构:

关键词: Newcastle disease virus;mitophagy;apoptosis;autophagy;cancer

期刊名称:ONCOTARGET ( 影响因子:5.168; 五年影响因子:5.312 )

ISSN: 1949-2553

年卷期: 2014 年 5 卷 15 期

页码:

收录情况: SCI

摘要: Apoptosis contributes to antitumor effect of Newcastle disease virus (NDV). Autophagy is a protective response under cellular stress including viral infection. How autophagy interferes with oncolysis of NDV remains unclear. In this study, we found that NDV La Sota strain induced autophagy and preserved autophagic flux in non-small cell lung cancer cells. NDV-induced autophagy promoted viral replication by blocking cancer cells from caspase-dependent apoptosis. Moreover, we found that NDV recruited SQSTM1-mediated mitophagy to control cytochrome c release, and thus blocked intrinsic pro-apoptotic signaling. Finally, we observed an enhanced oncolysis in NSCLC cells treated with NDV in the presence of an autophagy inhibitor 3-methyladenine (3-MA). Interestingly, a more profound antitumor effect could be achieved when administration of 3-MA was postponed to 24 h after NDV infection. Our findings unveil a novel way that NDV subverts mitophagy to favor its replication by blocking apoptosis, and provide rationale for systemic therapeutic cohort combining NDV with autophagy inhibitors in cancer therapy.

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