Genomic instability in mutant p53 cancer cells upon entotic engulfment.
Le Quesne, J
AffiliationMRC Toxicology Unit, Lancaster Road, Leicester, LE1 9HN, UK
MetadataShow full item record
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.
CitationGenomic instability in mutant p53 cancer cells upon entotic engulfment. 2018, 9(1): 3070 Nat Commun
- NKX2-1-mediated p53 expression modulates lung adenocarcinoma progression via modulating IKKβ/NF-κB activation.
- Authors: Chen PM, Wu TC, Cheng YW, Chen CY, Lee H
- Issue date: 2015 Jun 10
- SLC25A1, or CIC, is a novel transcriptional target of mutant p53 and a negative tumor prognostic marker.
- Authors: Kolukula VK, Sahu G, Wellstein A, Rodriguez OC, Preet A, Iacobazzi V, D'Orazi G, Albanese C, Palmieri F, Avantaggiati ML
- Issue date: 2014 Mar 15
- Molecular alterations and lung tumors in p53 mutant mice exposed to cigarette smoke.
- Authors: De Flora S, Balansky RM, D'Agostini F, Izzotti A, Camoirano A, Bennicelli C, Zhang Z, Wang Y, Lubet RA, You M
- Issue date: 2003 Feb 15
- Lung tumors with distinct p53 mutations respond similarly to p53 targeted therapy but exhibit genotype-specific statin sensitivity.
- Authors: Turrell FK, Kerr EM, Gao M, Thorpe H, Doherty GJ, Cridge J, Shorthouse D, Speed A, Samarajiwa S, Hall BA, Griffiths M, Martins CP
- Issue date: 2017 Jul 1
- LKB1 loss by alteration of the NKX2-1/p53 pathway promotes tumor malignancy and predicts poor survival and relapse in lung adenocarcinomas.
- Authors: Tsai LH, Chen PM, Cheng YW, Chen CY, Sheu GT, Wu TC, Lee H
- Issue date: 2014 Jul 17