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

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.