Journal
ONCOTARGET
Volume 5, Issue 15, Pages 6365-6374Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.2219
Keywords
Newcastle disease virus; mitophagy; apoptosis; autophagy; cancer
Categories
Funding
- National Natural Science Foundation of China [81071860, 81172143, 81372455, 81201621]
- Jiangsu Special Program for Clinical Medical Science and Technology [BL2014054]
- grant for outstanding physicians in Jiangsu Province
- Ph.D. Programs Foundation of Ministry of Education of China [20110091120032]
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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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