Oncolytic Newcastle disease virus promotes tumor cell death via the anoikis effector Bit1 translocation

Yang Qu; Sainan He; Liya Shen; Ying Liao; Xusheng Qiu; Lei Tan; Cuiping Song; Ning Tang; Yingjie Sun; Chan Ding

doi:10.1016/j.virs.2025.10.004

October 2025

Yang Qu, Sainan He, Liya Shen, Ying Liao, Xusheng Qiu, Lei Tan, Cuiping Song, Ning Tang, Yingjie Sun and Chan Ding. Oncolytic Newcastle disease virus promotes tumor cell death via the anoikis effector Bit1 translocation[J]. Virologica Sinica, 2025, 40(5): 842-852. doi: 10.1016/j.virs.2025.10.004

Citation: Yang Qu, Sainan He, Liya Shen, Ying Liao, Xusheng Qiu, Lei Tan, Cuiping Song, Ning Tang, Yingjie Sun, Chan Ding. Oncolytic Newcastle disease virus promotes tumor cell death via the anoikis effector Bit1 translocation .VIROLOGICA SINICA, 2025, 40(5) : 842-852. http://dx.doi.org/10.1016/j.virs.2025.10.004

溶瘤性新城疫病毒通过失巢凋亡效应蛋白Bit1易位促进肿瘤细胞死亡

屈阳 ^b ,
贺赛男 ^b ,
沈丽雅 ^b,c ,
廖瑛 ^b ,
仇旭升 ^b ,
谭磊 ^b ,
宋翠萍 ^b ,
唐宁 ^b ,
孙英杰 ^b,, ,
丁铲 ^a,b,,

a 上海交通大学农业与生物学院;
b. 中国农业科学院上海兽医研究所;
c. 广西大学动物科技学院

通讯作者： 孙英杰, sunyingjie@shvri.ac.cn; 丁铲, shoveldeen@sjtu.edu.cn
收稿日期： 2025-05-30
录用日期： 2025-10-15

摘要

失巢凋亡是一种由细胞脱离细胞外基质触发的特殊程序性死亡。对失巢凋亡产生抵抗力的肿瘤细胞能够获得脱离、迁移并定植远端部位的能力，最终导致肿瘤转移。Bit1（Bcl-2转录抑制因子1）作为失巢凋亡的关键效应分子，在细胞黏附缺失时被释放至胞质，并通过激活caspase非依赖途径诱导细胞凋亡。新城疫病毒（NDV）是一种对家禽业构成重大威胁的病原体，同时也是一种能选择性靶向并杀伤肿瘤细胞的溶瘤病毒。然而，NDV能否通过激活Bit1诱导抗失巢凋亡的肿瘤细胞发生死亡尚不明确。本研究通过物理方法诱导肿瘤细胞悬浮作为失巢凋亡的阳性对照，同时检测NDV感染肿瘤细胞后Bit1的表达及亚细胞定位变化。结果显示，病毒感染与细胞悬浮均引起肿瘤细胞死亡，同时诱导Bit1从线粒体向胞质转位且Bit1蛋白表达水平下降。值得注意的是，Bit1表达对病毒复制无显著影响。这些发现表明，NDV感染通过激活Bit1易位促进肿瘤细胞死亡，该过程与细胞悬浮诱导的失巢凋亡具有相似效应。此外，体内实验证实NDV能有效抑制小鼠黑色素瘤的转移与生长，而肿瘤细胞中过表达Bit1可加速这一进程。本研究为阐释NDV诱导肿瘤细胞死亡的机制提供了新视角，并为理解溶瘤病毒作用机制提供了潜在靶点
- 新城疫病毒
- , 溶瘤病毒
- , 细胞悬浮
- , 失巢凋亡
- , Bit1

Oncolytic Newcastle disease virus promotes tumor cell death via the anoikis effector Bit1 translocation

Yang Qu ^b ,
Sainan He ^b ,
Liya Shen ^b,c ,
Ying Liao ^b ,
Xusheng Qiu ^b ,
Lei Tan ^b ,
Cuiping Song ^b ,
Ning Tang ^b ,
Yingjie Sun ^b,, ,
Chan Ding ^a,b,,

a. School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, 200240, China;
b. Department of Avian Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai, 200241, China;
c. College of Animal Science and Technology, Guangxi University, Nanning, 530004, China

Corresponding author: Yingjie Sun, sunyingjie@shvri.ac.cn Chan Ding, shoveldeen@sjtu.edu.cn
Received Date: 30 May 2025
Accepted Date: 15 October 2025

Abstract

Anoikis is a specialized form of programmed cell death triggered by the detachment of cells from the extracellular matrix (ECM). Tumor cells that develop resistance to anoikis acquire the ability to detach, migrate, and colonize distant sites, ultimately leading to the formation of metastatic tumors. Bit1 (Bcl-2 inhibitor of transcription 1), a key effector of anoikis, is released into the cytoplasm upon loss of cell attachment and activates a caspase-independent pathway of apoptosis. Newcastle disease virus (NDV), a pathogen that poses a significant threat to the poultry industry, has also emerged as a promising oncolytic virus capable of selectively targeting and killing tumor cells. However, whether NDV can induce the death of anoikis-resistant tumor cells by activating Bit1 remains unclear. In this study, we utilized physical methods to induce cell suspension as a positive control for anoikis and further examined the expression and cellular localization of Bit1 following NDV infection in tumor cells. The results indicated that both viral infection and cell suspension resulted in partial cell death, accompanied by the translocation of Bit1 from the mitochondria to the cytoplasm and a reduction in its protein levels. Notably, Bit1 expression was found not to significantly affect viral replication. These findings suggest that NDV infection promotes tumor cell death by activating Bit1 translocation, mirroring the effects observed during cell suspension-induced anoikis. In addition, in vivo experiments demonstrated that NDV effectively inhibits the metastasis and growth of melanoma in mice, and that overexpression of Bit1 in tumor cells accelerates this process. This study provides novel insights into NDV-induced tumor cell death and identifies potential targets for understanding the mechanisms of oncolytic virus action.
- Newcastle disease virus (NDV)
- , Oncolytic virus
- , Cell suspension
- , Anoikis
- , Bit1

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