Genomic instability in mutant p53 cancer cells upon entotic engulfment.
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Authors
Mackay, HMoore, D
Hall, Callum
Birkbak, N
Jamal-Hanjani, M
Karim, S
Phatak, V
Piñon, L
Morton, J
Swanton, C
Le Quesne, J
Muller, P
Affiliation
MRC Toxicology Unit, Lancaster Road, Leicester, LE1 9HN, UKIssue Date
2018-08-03
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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 CommunJournal
Nature CommunicationsDOI
10.1038/s41467-018-05368-1PubMed ID
30076358Type
ArticleLanguage
enISSN
2041-1723ae974a485f413a2113503eed53cd6c53
10.1038/s41467-018-05368-1
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