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    Genomic instability in mutant p53 cancer cells upon entotic engulfment.

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    Authors
    Mackay, H
    Moore, D
    Hall, Callum
    Birkbak, N
    Jamal-Hanjani, M
    Karim, S
    Phatak, V
    Piñon, L
    Morton, J
    Swanton, C
    Le Quesne, J
    Muller, P
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    Affiliation
    MRC Toxicology Unit, Lancaster Road, Leicester, LE1 9HN, UK
    Issue Date
    2018-08-03
    
    Metadata
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    Abstract
    Cell-in-cell (CIC) structures are commonly seen in tumours. Their biological significance remains unclear, although they have been associated with more aggressive tumours. Here we report that mutant p53 promotes CIC via live cell engulfment. Engulfed cells physically interfere in cell divisions of host cells and for cells without p53 this leads to host cell death. In contrast, mutant p53 host cells survive, display aberrant divisions, multinucleation and tripolar mitoses. In xenograft studies, CIC-rich p53 mutant/null co-cultures show enhanced tumour growth. Furthermore, our results show that CIC is common within lung adenocarcinomas, is an independent predictor of poor outcome and disease recurrence, is associated with mutant p53 expression and correlated to measures of heterogeneity and genomic instability. These findings suggest that pro-tumorigenic entotic engulfment activity is associated with mutant p53 expression, and the two combined are a key factor in genomic instability.
    Citation
    Genomic instability in mutant p53 cancer cells upon entotic engulfment. 2018, 9(1): 3070 Nat Commun
    Journal
    Nature Communications
    URI
    http://hdl.handle.net/10541/621171
    DOI
    10.1038/s41467-018-05368-1
    PubMed ID
    30076358
    Type
    Article
    Language
    en
    ISSN
    2041-1723
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41467-018-05368-1
    Scopus Count
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