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Survivin protects fused cancer cells from massive cell death
Mihyang Do1,2,3, In-Hae Kwak1, Ju-Hyun Ahn1,2,3, In Jeong Lee1, Jae-Ho Lee1,2,3,*
1Department of Biochemistry and Molecular Biology, Ajou University School of Medicine,
2Department of Biomedical Sciences, The Graduate School, Ajou University,
3Genomic instability Research Center, Ajou University School of Medicine
Abstract
Tetraploidy, a potential precursor of cancer-associated aneuploidy, is produced either by cell fusion or cytokinesis failure. Here, we used low p53-expressing HeLa cells to address the fate of cancer cells after fusion. We found that massive cell death or growth arrest occurred a few days after fusion. Interestingly, cells with larger nuclei preferentially died after fusion, suggesting that a larger deviation of DNA content is a strong inducer of apoptosis. Notably, a fraction of cells escaped cell death. It turned out that the stability of survivin was increased, and its localization changed preferentially to the cytosol in fused cells. Knockdown of survivin decreased survival more in fused cells than in unfused ones, showing more dependency of fused cells on survivin. Collectively, after cancer cell fusion, some fused cells can avoid apoptotic crisis partly owing to survivin and proliferate continuously, a process that might contribute to human cancer progression.
Abstract, Accepted Manuscript(in press) [Submitted on October 28, 2016, Accepted on February 14, 2017]
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