Recombinant measles virus equipped with BNiP3, a pro-apoptotic gene, targets β-catenin pathway in triple negative breast cancer cells

Abstract

Oncolytic virotherapy is an emerging cancer therapy using genetically modified viruses. We previously reported engineering of measles virus with BNiP3, a proapoptotic gene for oncolytic purposes. The recombinant virus had shown promising results in breast cancer cells with a bias towards TNBC, an invasive and an aggressive subtype. Here, we investigated the mechanistic insights of anti-tumor effects induced by the recombinant virus. Initially, TNBC and non-TNBC tumor cell lines were compared bioinformatically using the available gene expression data through protein-protein interaction network using different topological properties. Four hub genes involved in tumor development and progression were identified to be the top genes in both the data sets. Of which, CTNNB1 gene encoding {beta}-catenin was found to be the significant one; as {beta}-catenin pathway is known to be a driver of tumor cell invasion and migration, the impact of the virus on this pathway was investigated in breast tumor cells. The results had demonstrated a notable decrease in {beta}-catenin expression and its downstream targets, cyclin D1, MMP7 reducing the migration potential of TNBC cells following virus infection. These findings suggest that the recombinant measles virus could be one of the effective treatment modalities to target invasive TNBC tumors. In vivo validation of engineered virus is ongoing to explore the therapeutic application of this virus. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=126 SRC="FIGDIR/small/718830v1_ufig1.gif" ALT="Figure 1"> View larger version (57K): org.highwire.dtl.DTLVardef@19d321dorg.highwire.dtl.DTLVardef@1450ebeorg.highwire.dtl.DTLVardef@cb191eorg.highwire.dtl.DTLVardef@1de2d16_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIUse of recombinant measles virus with a pro-apoptotic gene, BNiP3 to target breast cancer cells C_LIO_LIIdentification of top regulatory genes in breast cancer development and progression C_LIO_LIReduction of {beta}-catenin expression encoded by CTNNB1 gene in TNBC cells following virus infection C_LIO_LIDownregulation of {beta}-catenin downstream targets in TNBC cells with virus infection C_LIO_LIInhibition of migratory potential of TNBC cells following infection C_LI