Newcastle-disease-virus-induced ferroptosis through nutrient deprivation and ferritinophagy in tumor cells
Xianjin Kan,
Yuncong Yin,
Cuiping Song,
Lei Tan,
Xusheng Qiu,
Ying Liao,
Weiwei Liu,
Songshu Meng,
Yingjie Sun,
Chan Ding
Affiliations
Xianjin Kan
Department of Avian Infectious Diseases, Shanghai Veterinary Research Institute. Chinese Academy of Agricultural Science, Shanghai 200241, P.R. China
Yuncong Yin
College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, Jiangsu Province, China
Cuiping Song
Department of Avian Infectious Diseases, Shanghai Veterinary Research Institute. Chinese Academy of Agricultural Science, Shanghai 200241, P.R. China
Lei Tan
Department of Avian Infectious Diseases, Shanghai Veterinary Research Institute. Chinese Academy of Agricultural Science, Shanghai 200241, P.R. China
Xusheng Qiu
Department of Avian Infectious Diseases, Shanghai Veterinary Research Institute. Chinese Academy of Agricultural Science, Shanghai 200241, P.R. China
Ying Liao
Department of Avian Infectious Diseases, Shanghai Veterinary Research Institute. Chinese Academy of Agricultural Science, Shanghai 200241, P.R. China
Weiwei Liu
Department of Avian Infectious Diseases, Shanghai Veterinary Research Institute. Chinese Academy of Agricultural Science, Shanghai 200241, P.R. China
Songshu Meng
Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, PR China
Yingjie Sun
Department of Avian Infectious Diseases, Shanghai Veterinary Research Institute. Chinese Academy of Agricultural Science, Shanghai 200241, P.R. China; Corresponding author
Chan Ding
Department of Avian Infectious Diseases, Shanghai Veterinary Research Institute. Chinese Academy of Agricultural Science, Shanghai 200241, P.R. China; College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, Jiangsu Province, China; Corresponding author
Summary: A number of new cell death processes have been discovered in recent years, including ferroptosis, which is characterized by the accumulation of lipid peroxidation products derived from iron metabolism. The evidence suggests that ferroptosis has a tumor-suppressor function. However, the mechanism by which ferroptosis mediates the response of tumor cells to oncolytic viruses remains poorly understood. The Newcastle disease virus (NDV) can selectively replicate in tumor cells. We show that NDV-induced ferroptosis acts through p53-SLC7A11-GPX4 pathway. Meanwhile, the levels of intracellular reactive oxygen species and lipid peroxides increased in tumor cells. Ferritinophagy was induced by NDV promotion of ferroptosis through the release of ferrous iron and an enhanced Fenton reaction. Collectively, these observations demonstrated that the NDV can kill tumor cells through ferroptosis. Our study provides novel insights into the mechanisms of NDV-induced ferroptosis and highlights the critical role of viruses in treating therapy-resistant cancers.
