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Defining the clonal dynamics leading to mouse skin tumour initiation

The changes that occur in cell dynamics following oncogenic mutation that lead to the development of tumours are currently unknown. Here, using skin epidermis as a model, we assessed the impact of oncogenic hedgehog signalling in distinct cell populations and their capacity to induce basal cell carc...

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Autores principales: Sánchez-Danés, Adriana, Hannezo, Edouard, Larsimont, Jean-Christophe, Liagre, Mélanie, Youssef, Khalil Kass, Simons, Benjamin D, Blanpain, Cédric
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5068560/
https://www.ncbi.nlm.nih.gov/pubmed/27459053
http://dx.doi.org/10.1038/nature19069
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author Sánchez-Danés, Adriana
Hannezo, Edouard
Larsimont, Jean-Christophe
Liagre, Mélanie
Youssef, Khalil Kass
Simons, Benjamin D
Blanpain, Cédric
author_facet Sánchez-Danés, Adriana
Hannezo, Edouard
Larsimont, Jean-Christophe
Liagre, Mélanie
Youssef, Khalil Kass
Simons, Benjamin D
Blanpain, Cédric
author_sort Sánchez-Danés, Adriana
collection PubMed
description The changes that occur in cell dynamics following oncogenic mutation that lead to the development of tumours are currently unknown. Here, using skin epidermis as a model, we assessed the impact 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, were competent to initiate tumour formation upon oncogenic hedgehog signalling. Interestingly, this difference was due to the hierarchical organization of tumour growth in oncogene-targeted stem cells, characterized by an increase of 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 not only dependent on their long-term survival and expansion, but also on the specific clonal dynamics of the cancer cell of origin.
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spelling pubmed-50685602017-02-18 Defining the clonal dynamics leading to mouse skin tumour initiation Sánchez-Danés, Adriana Hannezo, Edouard Larsimont, Jean-Christophe Liagre, Mélanie Youssef, Khalil Kass Simons, Benjamin D Blanpain, Cédric Nature Article The changes that occur in cell dynamics following oncogenic mutation that lead to the development of tumours are currently unknown. Here, using skin epidermis as a model, we assessed the impact 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, were competent to initiate tumour formation upon oncogenic hedgehog signalling. Interestingly, this difference was due to the hierarchical organization of tumour growth in oncogene-targeted stem cells, characterized by an increase of 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 not only dependent on their long-term survival and expansion, but also on the specific clonal dynamics of the cancer cell of origin. 2016-08-18 /pmc/articles/PMC5068560/ /pubmed/27459053 http://dx.doi.org/10.1038/nature19069 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Sánchez-Danés, Adriana
Hannezo, Edouard
Larsimont, Jean-Christophe
Liagre, Mélanie
Youssef, Khalil Kass
Simons, Benjamin D
Blanpain, Cédric
Defining the clonal dynamics leading to mouse skin tumour initiation
title Defining the clonal dynamics leading to mouse skin tumour initiation
title_full Defining the clonal dynamics leading to mouse skin tumour initiation
title_fullStr Defining the clonal dynamics leading to mouse skin tumour initiation
title_full_unstemmed Defining the clonal dynamics leading to mouse skin tumour initiation
title_short Defining the clonal dynamics leading to mouse skin tumour initiation
title_sort defining the clonal dynamics leading to mouse skin tumour initiation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5068560/
https://www.ncbi.nlm.nih.gov/pubmed/27459053
http://dx.doi.org/10.1038/nature19069
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