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dc.contributor.authorMackay, H
dc.contributor.authorMoore, D
dc.contributor.authorHall, Callum
dc.contributor.authorBirkbak, N
dc.contributor.authorJamal-Hanjani, M
dc.contributor.authorKarim, S
dc.contributor.authorPhatak, V
dc.contributor.authorPiñon, L
dc.contributor.authorMorton, J
dc.contributor.authorSwanton, C
dc.contributor.authorLe Quesne, J
dc.contributor.authorMuller, P
dc.date.accessioned2018-08-19T14:02:44Z
dc.date.available2018-08-19T14:02:44Z
dc.date.issued2018-08-03
dc.identifier.citationGenomic instability in mutant p53 cancer cells upon entotic engulfment. 2018, 9(1): 3070 Nat Communen
dc.identifier.issn2041-1723
dc.identifier.pmid30076358
dc.identifier.doi10.1038/s41467-018-05368-1
dc.identifier.urihttp://hdl.handle.net/10541/621171
dc.description.abstractCell-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.
dc.language.isoenen
dc.rightsArchived with thanks to Nature communicationsen
dc.titleGenomic instability in mutant p53 cancer cells upon entotic engulfment.en
dc.typeArticleen
dc.contributor.departmentMRC Toxicology Unit, Lancaster Road, Leicester, LE1 9HN, UKen
dc.identifier.journalNature Communicationsen
refterms.dateFOA2018-12-17T15:29:47Z
html.description.abstractCell-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.


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