Serving the Society Since 1986
Advanced Search
Volume 40 Issue 5
October 2025
    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
    shu

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

    • 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

    • 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.
    • 加载中

      1. Ampomah, P.B.,Lim, L.H.K., 2020. Influenza A virus-induced apoptosis and virus propagation. Apoptosis, 25, 1-11.

      2. Biliran, H., Jan, Y.W., Chen, R.W., Pasquale, E.B.,Ruoslahti, E., 2008. Protein kinase D is a positive regulator of Bit1 apoptotic function. Journal of Biological Chemistry, 283, 28029-28037.

      3. Bommareddy, P.K., Shettigar, M.,Kaufman, H.L., 2018. Integrating oncolytic viruses in combination cancer immunotherapy. Nature Reviews Immunology, 18, 498-513.

      4. Bondar, V.M.,Mcconkey, D.J., 2002. Anoikis is regulated by BCL-2-Independent pathways in human prostate carcinoma cells. Prostate, 51, 42-49.

      5. Brunquell, C., Biliran, H., Jennings, S., Ireland, S.K., Chen, R.W.,Ruoslahti, E., 2012. TLE1 Is an Anoikis Regulator and Is Downregulated by Bit1 in Breast Cancer Cells. Molecular Cancer Research, 10, 1482-1495.

      6. Chen, Y., Zhu, S.S., Liao, T.X., Wang, C.X., Han, J.J., Yang, Z.Y., Lu, X.L., Hu, Z.L., Hu, J., Wang, X.Q., Gu, M., Gao, R.Y., Liu, K.T., Liu, X.W., Ding, C., Hu, S.L.,Liu, X.F., 2024. The HN protein of Newcastle disease virus induces cell apoptosis through the induction of lysosomal membrane permeabilization. Plos Pathogens, 20, e1011981.

      7. De Pereda, J.M., Waas, W.F., Jan, Y.W., Ruoslahti, E., Schimmel, P.,Pascual, J., 2004. Crystal structure of a human peptidyl-tRNA hydrolase reveals a new fold and suggests basis for a bifunctional activity. Journal of Biological Chemistry, 279, 8111-8115.

      8. Everett, H.,Mcfadden, G., 1999. Apoptosis: an innate immune response to virus infection. Trends in Microbiology, 7, 160-165.

      9. Fan, T.L., Tian, F., Yi, S.Y., Ke, Y., Han, S.N., Zhang, L.R.,Liu, H.T., 2014. Implications of Bit1 and AIF overexpressions in esophageal squamous cell carcinoma. Tumor Biology, 35, 519-527.

      10. Frisch, S.M., 1996. Hot papers - Cell biology/apoptosis - Disruption of epithelial cell-matrix interactions induces apoptosis by S.M. Frisch, H. Francis - Comments. Scientist, 10, 14-14.

      11. Gilmore, A.P., 2005. Anoikis. Cell Death and Differentiation, 12, 1473-1477.

      12. Griffiths, G.S., Grundl, M., Leychenko, A., Reiter, S., Young-Robbins, S.S., Sulzmaier, F.J., Caliva, M.J., Ramos, J.W.,Matter, M.L., 2011. Bit-1 Mediates Integrin-dependent Cell Survival through Activation of the NFκB Pathway. Journal of Biological Chemistry, 286, 14713-14723.

      13. Grossmann, J., 2002. Molecular mechanisms of "detachment-induced apoptosis-Anoikis". Apoptosis, 7, 247-260.

      14. Han, Y.H., Wang, Y., Lee, S.J., Jin, M.H., Sun, H.N.,Kwon, T., 2023. Regulation of anoikis by extrinsic death receptor pathways. Cell Communication and Signaling, 21, 227.

      15. Jan, Y.W., Matter, M., Pai, J.T., Chen, Y.L., Pilch, J., Komatsu, M., Ong, E., Fukuda, M.,Ruoslahti, E., 2004. A mitochondrial protein, Bit1, mediates apoptosis regulated by integrins and Groucho/TLE corepressors. Cell, 116, 751-762.

      16. Jiang, H., Qu, Y., Kan, X.J., Yang, M.Q., Gong, Y.B., Liao, Y., Qiu, X.S., Tan, L., Song, C.P., Nair, V., Ding, C.,Sun, Y.J., 2025. Pexophagy-driven redox imbalance promotes virus-induced ferroptosis. Cell Reports, 44, 115783.

      17. Kakavandi, E., Shahbahrami, R., Goudarzi, H., Eslami, G.,Faghihloo, E., 2018. Anoikis resistance and oncoviruses. Journal of Cellular Biochemistry, 119, 2484-2491.

      18. Kan, X.J., Yin, Y.C., Song, C.P., Tan, L., Qiu, X.S., Liao, Y., Liu, W.W., Meng, S.S., Sun, Y.J.,Ding, C., 2021. Newcastle-disease-virus-induced ferroptosis through nutrient deprivation and ferritinophagy in tumor cells. Iscience, 24, 102837.

      19. Karmali, P.P., Brunquell, C., Tram, H., Ireland, S.K., Ruoslahti, E.,Biliran, H., 2011. Metastasis of Tumor Cells Is Enhanced by Downregulation of Bit1. Plos One, 6, e23840.

      20. Kim, B.G., Gao, M.Q., Choi, Y.P., Kang, S., Park, H.R., Kang, K.S.,Cho, N.H., 2012. Invasive breast cancer induces laminin-332 upregulation and integrin β4 neoexpression in myofibroblasts to confer an anoikis-resistant phenotype during tissue remodeling. Breast Cancer Research, 14, R88.

      21. Li, Y.R., Jiang, W.Y., Niu, Q.N., Sun, Y.J., Meng, C.C., Tan, L., Song, C.P., Qiu, X.S., Liao, Y.,Ding, C., 2019. eIF2α-CHOP-BCl-2/JNK and IRE1α-XBP1/JNK signaling promote apoptosis and inflammation and support the proliferation of Newcastle disease virus. Cell Death & Disease, 10, 891.

      22. Massague, J.,Obenauf, A.C., 2016. Metastatic colonization by circulating tumour cells. Nature, 529, 298-306.

      23. Providence, K.M., Higgins, S.P., Mullen, A., Battista, A., Samarakoon, R., Higgins, C.E., Wilkins-Port, C.E.,Higgins, P.J., 2008. SERPINE1 (PAI-1) is deposited into keratinocyte migration "trails" and required for optimal monolayer wound repair. Archives of Dermatological Research, 300, 303-310.

      24. Qu, Y., Wang, S.Y., Jiang, H., Liao, Y., Qiu, X.S., Tan, L., Song, C.P., Nair, V., Yang, Z.Q., Sun, Y.J.,Ding, C., 2024. Newcastle disease virus infection induces parthanatos in tumor cells via calcium waves. Plos Pathogens, 20, e1012737.

      25. Rytomaa, M., Martins, L.M.,Downward, J., 1999. Involvement of FADD and caspase-8 signalling in detachment-induced apoptosis. Current Biology, 9, 1043-1046.

      26. Sinkovics, J.G.,Horvath, J.C., 2000. Newcastle disease virus (NDV): brief history of its oncolytic strains. Journal of Clinical Virology, 16, 1-15.

      27. Sun, Y.F., Tang, L.L., Kan, X.J., Tan, L., Song, C.P., Qiu, X.S., Liao, Y., Nair, V., Ding, C., Liu, X.F.,Sun, Y.J., 2024. Oncolytic Newcastle disease virus induced degradation of YAP through E3 ubiquitin ligase PRKN to exacerbate ferroptosis in tumor cells. Journal of Virology, 98, e0189723.

      28. Turpin, J., El Safadi, D., Lebeau, G., Krejbich, M., Chatelain, C., Despres, P., Viranaicken, W.,Krejbich-Trotot, P., 2022. Apoptosis during ZIKA Virus Infection: Too Soon or Too Late? International Journal of Molecular Sciences, 23, 1287.

      29. Wang, Y.M., Cheng, S.H., Chen, J.C., Fleishman, J.S., Tang, H.L., Chen, Z.S., Chen, W.K.,Ding, M.C., 2024. Targeting anoikis resistance as a strategy for cancer therapy. Drug Resistance Updates, 75, 101099.

      30. Wang, Y.M., Cheng, S.H., Chen, J.C., Fleishman, J.S., Tang, H.L., Chen, Z.S., Chen, W.K.,Ding, M.C., 2024. Targeting anoikis resistance as a strategy for cancer therapy. Drug Resistance Updates, 75, 101099.

      31. Yao, X., Jennings, S., Ireland, S.K., Pham, T., Temple, B., Davis, M., Chen, R.W., Davenport, I.,Biliran, H., 2014. The Anoikis Effector Bit1 Displays Tumor Suppressive Function in Lung Cancer Cells. Plos One, 9, e101564.

      32. Zhang, C.L., Wang, Y., Zhen, Z.F., Li, J.Y., Su, J.,Wu, C.Y., 2024. mTORC1 Mediates Biphasic Mechano-Response to Orchestrate Adhesion-Dependent Cell Growth and Anoikis Resistance. Advanced Science, 11, e2307206.

      33. Zhang, D., Ding, Z.,Xu, X.H., 2023. Pathologic Mechanisms of the Newcastle Disease Virus. Viruses-Basel, 15, 864.

      34. Zhong, L.P., Gan, L., Wang, B., Wu, T., Yao, F., Gong, W.L., Peng, H.M., Deng, Z.M., Xiao, G.Y., Liu, X.Y., et al., 2025. Hyperacute rejection-engineered oncolytic virus for interventional clinical trial in refractory cancer patients. Cell, 188, 1119-1136.

    • 加载中

    Figures(1)

    PDF

    Article Metrics

    Article views(560) PDF downloads(7) Cited by()

    Related
    Proportional views

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

        Corresponding author: Yingjie Sun, sunyingjie@shvri.ac.cn
        Corresponding author: Chan Ding, shoveldeen@sjtu.edu.cn
      • 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
      • 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.

        HTML

      Figure (1)  Reference (34) Relative (20)

      目录

      This journal is a member of, and subscribes to the principles of, the Committee on Publication Ethics (COPE)

      鄂ICP备05001977号

         

      鄂公网安备 42010602003674号

      Copyright © 2019 Virologica Sinica. All rights reserved

      /

      DownLoad:  Full-Size Img  PowerPoint
      Return
      Return