Journal
ONCOTARGET
Volume 5, Issue 11, Pages 3907-3918Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.2028
Keywords
oncolytic measles virus; non-small cell lung cancer; autophagy; mitophagy; apoptosis; necrosis
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Funding
- National Natural Science Foundation of China [81071860, 81172143, 81301943]
- Fundamental Research Funds for the Central Universities [1093021412, 1112021402]
- State Key Laboratory of Pharmaceutical Biotechnology [KF-GN-201410]
- Scientific Foundation of Graduate School of Nanjing University
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Although apoptotic phenomena have been observed in malignant cells infected by measles virus vaccine strain Edmonston B (MV-Edm), the precise oncolytic mechanisms are poorly defined. In this study we found that MV-Edm induced autophagy and sequestosome 1-mediated mitophagy leading to decreased cytochrome c release, which blocked the pro-apoptotic cascade in non-small cell lung cancer cells (NSCLCs). The decrease of apoptosis by mitophagy favored viral replication. Persistent viral replication sustained by autophagy ultimately resulted in necrotic cell death due to ATP depletion. Importantly, when autophagy was impaired in NSCLCs MV-Edm-induced cell death was significantly abrogated despite of increased apoptosis. Taken together, our results define a novel oncolytic mechanism by which mitophagy switches cell death from apoptosis to more efficient necrosis in NSCLCs following MV-Edm infection. This provides a foundation for future improvement of oncolytic virotherapy or antiviral therapy.
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