Genomic instability in mutant p53 cancer cells upon entotic engulfment
More about Open Access at the CrickAuthors list
Hannah L Mackay David Moore Callum Hall Nicolai Birkbak Mariam Jamal-Hanjani Saadia A Karim Vinaya M Phatak Lucia Piñon Jennifer P Morton Charles Swanton John Le Quesne Patricia AJ MullerAbstract
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.
Journal details
Journal Nature Communications
Volume 9
Issue number 1
Pages 3070
Available online
Publication date
Full text links
Publisher website (DOI) 10.1038/s41467-018-05368-1
Figshare View on figshare
Europe PubMed Central 30076358
Pubmed 30076358