Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/44814
Title: Genomic instability in mutant p53 cancer cells upon entotic engulfment
Authors: Mackay, HL
Moore, D
Hall, C
Birkbak, NJ
Jamal-Hanjani, M
Karim, SA
Phatak, VM
Pinon, L
Morton, JP
Swanton, C
Le Quesne, J
Muller, PAJ
First Published: 3-Aug-2018
Publisher: Nature Research (part of Springer Nature)
Citation: Nature Communications, 2018, 9, Article number: 3070
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.
DOI Link: 10.1038/s41467-018-05368-1
ISSN: 2041-1723
Links: https://www.nature.com/articles/s41467-018-05368-1
http://hdl.handle.net/2381/44814
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © the authors, 2018. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Description: The original version of this article incorrectly omitted an affiliation of Patricia A. J. Muller: ‘Cancer Research UK Manchester Institute, The University of Manchester | Alderley Park, Manchester, SK10 4TG, UK’. This has been corrected in both the PDF and HTML versions of the article. https://www.nature.com/articles/s41467-018-06026-2
Appears in Collections:Published Articles, Dept. of Cancer Studies and Molecular Medicine

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