Genomic instability in mutant p53 cancer cells upon entotic engulfment

Mackay, H. L. et al. (2018) Genomic instability in mutant p53 cancer cells upon entotic engulfment. Nature Communications, 9(1), 3070. (doi: 10.1038/s41467-018-05368-1) (PMID:30076358) (PMCID:PMC6076230)

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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.

Item Type:Articles
Additional Information:P.M. and J.L.Q. are supported by the MRC Toxicology Unit programme funding. P.M. is funded through a Sir Henry Dale fellowship from the Wellcome Trust and the Royal Society.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Le Quesne, Professor John and Morton, Professor Jen and Karim, Ms Saadia
Authors: Mackay, H. L., Moore, D., Hall, C., Birkbak, N. J., Jamal-Hanjani, M., Karim, S. A., Phatak, V. M., Piñon, L., Morton, J. P., Swanton, C., Le Quesne, J., and Muller, P. A.J.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Nature Communications
Publisher:Nature Publishing Group
ISSN:2041-1723
ISSN (Online):2041-1723
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Nature Communications 9(1):3070
Publisher Policy:Reproduced under a Creative Commons License
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