Defining the clonal dynamics leading to mouse skin tumour initiation Journal Article

Author(s): Sánchez-Danés, Adriana; Hannezo, Edouard; Larsimont, Jean Christophe; Liagre, Mélanie; Youssef, Khalil K; Simons, Benjamin D; Blanpain, Cédric D
Article Title: Defining the clonal dynamics leading to mouse skin tumour initiation
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.
Journal Title: Nature
Volume: 536
Issue 7616
ISSN: 0028-0836
Publisher: Nature Publishing Group  
Date Published: 2016-07-08
Start Page: 298
End Page: 303
DOI: 10.1038/nature19069
Notes: We would like to thank J.-M. Vanderwinden and the LiMiF for the help with confocal microscopy. C.B. is an investigator of WELBIO. A.S.-D. and J.C.L. are supported by a fellowship of the FNRS and FRIA respectively. B.D.S. and E.H. are supported by the Wellcome Trust (grant numbers 098357/Z/12/Z and 110326/Z/15/Z). E.H. is supported by a fellowship from Trinity College, Cambridge. This work was supported by the FNRS, the IUAP program, the Fondation contre le Cancer, the ULB fondation, the foundation Bettencourt Schueller, the foundation Baillet Latour, a consolidator grant of the European Research Council.
Open access: no