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Genomic instability in mutant p53 cancer cells upon entotic engulfment

Author

Listed:
  • Hannah L. Mackay

    (MRC Toxicology Unit
    University of Birmingham)

  • David Moore

    (MRC Toxicology Unit
    University of Leicester)

  • Callum Hall

    (Cancer Research UK Manchester Institute)

  • Nicolai J. Birkbak

    (The Francis Crick Institute
    University College London Cancer Institute)

  • Mariam Jamal-Hanjani

    (University College London Hospitals
    Garscube Estate)

  • Saadia A. Karim

    (University of Glasgow)

  • Vinaya M. Phatak

    (MRC Toxicology Unit)

  • Lucia Piñon

    (MRC Toxicology Unit)

  • Jennifer P. Morton

    (University of Glasgow
    University Hospitals Leicester NHS Trust)

  • Charles Swanton

    (The Francis Crick Institute
    University College London Cancer Institute
    University College London Hospitals)

  • John Quesne

    (MRC Toxicology Unit
    University of Leicester
    University Hospitals Leicester NHS Trust)

  • Patricia A. J. Muller

    (MRC Toxicology Unit
    Cancer Research UK Manchester Institute)

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.

Suggested Citation

  • Hannah L. Mackay & David Moore & Callum Hall & Nicolai J. Birkbak & Mariam Jamal-Hanjani & Saadia A. Karim & Vinaya M. Phatak & Lucia Piñon & Jennifer P. Morton & Charles Swanton & John Quesne & Patri, 2018. "Genomic instability in mutant p53 cancer cells upon entotic engulfment," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05368-1
    DOI: 10.1038/s41467-018-05368-1
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    Cited by:

    1. Noelle A. Sterling & Jun Young Park & Raehee Park & Seo-Hee Cho & Seonhee Kim, 2023. "An entosis-like process induces mitotic disruption in Pals1 microcephaly pathogenesis," Nature Communications, Nature, vol. 14(1), pages 1-10, December.

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