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Defining the clonal dynamics leading to mouse skin tumour initiation

Author

Listed:
  • Adriana Sánchez-Danés

    (Université Libre de Bruxelles, IRIBHM)

  • Edouard Hannezo

    (Cavendish Laboratory, J. J. Thomson Avenue
    The Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge
    Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge)

  • Jean-Christophe Larsimont

    (Université Libre de Bruxelles, IRIBHM)

  • Mélanie Liagre

    (Université Libre de Bruxelles, IRIBHM)

  • Khalil Kass Youssef

    (Université Libre de Bruxelles, IRIBHM)

  • Benjamin D. Simons

    (Cavendish Laboratory, J. J. Thomson Avenue
    The Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge
    Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge)

  • Cédric Blanpain

    (Université Libre de Bruxelles, IRIBHM
    WELBIO, Université Libre de Bruxelles)

Abstract

The changes in cell dynamics after oncogenic mutation that lead to the development of tumours are currently unknown. Here, using skin epidermis as a model, we assessed the effect of oncogenic hedgehog signalling in distinct cell populations and their capacity to induce basal cell carcinoma, the most frequent cancer in humans. We found that only stem cells, and not progenitors, initiated tumour formation upon oncogenic hedgehog signalling. This difference was due to the hierarchical organization of tumour growth in oncogene-targeted stem cells, characterized by an increase in symmetric self-renewing divisions and a higher p53-dependent resistance to apoptosis, leading to rapid clonal expansion and progression into invasive tumours. Our work reveals that the capacity of oncogene-targeted cells to induce tumour formation is dependent not only on their long-term survival and expansion, but also on the specific clonal dynamics of the cancer cell of origin.

Suggested Citation

  • Adriana Sánchez-Danés & Edouard Hannezo & Jean-Christophe Larsimont & Mélanie Liagre & Khalil Kass Youssef & Benjamin D. Simons & Cédric Blanpain, 2016. "Defining the clonal dynamics leading to mouse skin tumour initiation," Nature, Nature, vol. 536(7616), pages 298-303, August.
    • Handle: RePEc:nat:nature:v:536:y:2016:i:7616:d:10.1038_nature19069
    DOI: 10.1038/nature19069
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    Cited by:

    1. Elle Koren & Alona Feldman & Marianna Yusupova & Avihay Kadosh & Egor Sedov & Roi Ankawa & Yahav Yosefzon & Waseem Nasser & Stefanie Gerstberger & Liam B. Kimel & Noa Priselac & Samara Brown & Sam Sha, 2022. "Thy1 marks a distinct population of slow-cycling stem cells in the mouse epidermis," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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