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cells, cell, cic, mutant, fig, pubmed, engulfment, article, cancer, google, scholar, supplementary, tumour, lung, cas, structures, tumours, entotic, expression, mice, host, number, engulfing, nature, null, genomic, death, data, adenocarcinoma, experiments, division, events, growth, movie, bar, stained, central, tripolar, study, scale, bars, status, left, red, sem, cocultures, observed, size, lines, images,

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nature portfolio privacy policy biomedical services crispr construct plv-u6g-epcg advertising cancer research uk john le quesne & patricia reprints cic-rich p53 mutant/null nature 511 nature 502 nature 545 nature 501 nature library supplementary movie 1 supplementary movie 2 supplementary movie 3 supplementary movie 4 supplementary movie 5 supplementary movie 6 supplementary movie 7 supplementary movie 8 supplementary movie 9 john le quesne high-risk invasive patterns mariam jamal-hanjani smooth/mild/moderate/severe european genome–phenome archive fresh media added research focusing treatment-resistant subclones resulting 5-arylamino-2h-pyrazol-3-yl grant number c11496/a17786 mutant p53/p53 null overcomes growth arrest/senescence epithelial-rich viable malignancy mutant p53-independent manner small-cell lung cancer �moon-shape’ host nucleus original author parametric mann–whitney test parametric kruskal–wallis test mutant p53-positive cells specifically detect p-chk1 k-ras12d activating mutation permissions wilcoxon rank-sum test high-risk histological patterns alphav-class integrins cooperate

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         headline:Genomic instability in mutant p53 cancer cells upon entotic engulfment
         description: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. Cell-in-cell (CIC) structures are frequently observed in cancers; however, it is unclear how their formation contributes to tumorigenesis. Here, the authors show that the high frequency of CIC is linked to mutant p53 status and CIC containing p53 mutant cancer cells are pro-tumorigenic due to enhanced genomic instability.
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      headline:Genomic instability in mutant p53 cancer cells upon entotic engulfment
      description: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. Cell-in-cell (CIC) structures are frequently observed in cancers; however, it is unclear how their formation contributes to tumorigenesis. Here, the authors show that the high frequency of CIC is linked to mutant p53 status and CIC containing p53 mutant cancer cells are pro-tumorigenic due to enhanced genomic instability.
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            address:
               name:MRC Toxicology Unit, Leicester, UK
               type:PostalAddress
            type:Organization
      name:Lucia Piñon
      affiliation:
            name:MRC Toxicology Unit
            address:
               name:MRC Toxicology Unit, Leicester, UK
               type:PostalAddress
            type:Organization
      name:Jennifer P. Morton
      affiliation:
            name: University of Glasgow
            address:
               name:Institute of Cancer Sciences, University of Glasgow, Glasgow, UK
               type:PostalAddress
            type:Organization
            name:University Hospitals Leicester NHS Trust
            address:
               name:Department of Histopathology, Glenfield Hospital, University Hospitals Leicester NHS Trust, Leicester, UK
               type:PostalAddress
            type:Organization
      name:Charles Swanton
      affiliation:
            name:The Francis Crick Institute
            address:
               name:Translational Cancer Therapeutics Laboratory, The Francis Crick Institute, London, UK
               type:PostalAddress
            type:Organization
            name:University College London Cancer Institute
            address:
               name:Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK
               type:PostalAddress
            type:Organization
            name:University College London Hospitals
            address:
               name:Department of Medical Oncology, University College London Hospitals, London, UK
               type:PostalAddress
            type:Organization
      name:John Le Quesne
      affiliation:
            name:MRC Toxicology Unit
            address:
               name:MRC Toxicology Unit, Leicester, UK
               type:PostalAddress
            type:Organization
            name:University of Leicester
            address:
               name:Cancer studies, University of Leicester, Leicester, UK
               type:PostalAddress
            type:Organization
            name:University Hospitals Leicester NHS Trust
            address:
               name:Department of Histopathology, Glenfield Hospital, University Hospitals Leicester NHS Trust, Leicester, UK
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Patricia A. J. Muller
      affiliation:
            name:MRC Toxicology Unit
            address:
               name:MRC Toxicology Unit, Leicester, UK
               type:PostalAddress
            type:Organization
            name:Cancer Research UK Manchester Institute
            address:
               name:Cancer Research UK Manchester Institute, Manchester, UK
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:MRC Toxicology Unit, Leicester, UK
      name:Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK
      name:MRC Toxicology Unit, Leicester, UK
      name:Cancer studies, University of Leicester, Leicester, UK
      name:Cancer Research UK Manchester Institute, Manchester, UK
      name:Translational Cancer Therapeutics Laboratory, The Francis Crick Institute, London, UK
      name:Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK
      name:Department of Medical Oncology, University College London Hospitals, London, UK
      name:CRUK The Beatson Institute, Garscube Estate, Glasgow, UK
      name:Institute of Cancer Sciences, University of Glasgow, Glasgow, UK
      name:MRC Toxicology Unit, Leicester, UK
      name:MRC Toxicology Unit, Leicester, UK
      name:Institute of Cancer Sciences, University of Glasgow, Glasgow, UK
      name:Department of Histopathology, Glenfield Hospital, University Hospitals Leicester NHS Trust, Leicester, UK
      name:Translational Cancer Therapeutics Laboratory, The Francis Crick Institute, London, UK
      name:Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK
      name:Department of Medical Oncology, University College London Hospitals, London, UK
      name:MRC Toxicology Unit, Leicester, UK
      name:Cancer studies, University of Leicester, Leicester, UK
      name:Department of Histopathology, Glenfield Hospital, University Hospitals Leicester NHS Trust, Leicester, UK
      name:MRC Toxicology Unit, Leicester, UK
      name:Cancer Research UK Manchester Institute, Manchester, UK

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