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Press Release
Brussels, 8th July 2016
Cancer : the stem cell dynamics
Publication in the accelerated article preview of Nature: researchers at the Université libre de
Bruxelles, ULB define for the first time the changes in the stem cell dynamics that lead to
tumor initiation.
One of the key questions in cancer biology is to identify the cancer cell of origin and
understand in these cells how oncogene alters their clonal dynamics and changes their
proliferation, cell death, balance between renewal and differentiation to induce tumor
development.
In a study published in Nature, researchers lead by Pr. Cédric Blanpain, MD/PhD, Welbio
investigator, and Professor at the Université Libre de Bruxelles, Belgium, in collaboration with
Pr. Benjamin D Simons, University of Cambridge,UK, demonstrated that the capacity of
oncogene-expressing cells to induce tumor formation depends on the clonal dynamics of the
cancer cell of origin.
Many cancers arise from tissues maintained by stem and progenitor cells that ultimately give
rise to non-dividing terminally differentiated cells. However, little is known about the
contribution of stem cells and progenitors to cancer initiation. During tumor initiation, cells
targeted by oncogenic mutations undergo a series of molecular changes leading to their
clonal expansion and the acquisition of invasive properties. How exactly oncogenic mutations
impact on the rate of stem cell and progenitor division, and change the proportion of divisions
that result in symmetric and asymmetric cell fate, allowing clonal expansion and tumor
progression is poorly understood.
In this new study published in Nature, Adriana Sánchez-Danés and colleagues define the
clonal dynamics that lead to skin cancer initiation using the basal cell carcinoma, the most
frequent tumor in humans, as a model. They used state of the art genetic mouse models to
activate the oncogene in stem cells and committed progenitor populations. Specifically, they
use a genetic tracing strategy that allowed them to mark the stem cells and committed
progenitors that express the oncogene and follow the fate of their progeny over time.
Interestingly, they found that only stem cells and not their progenitor cell progeny were
competent to initiate tumor formation upon oncogenic activation. “It was particularly exciting
to observe that progenitor-derived clones grew in size but eventually became frozen in a pre-
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tumorigenic state while stem cell-derived clones expanded rapidly leading in time to basal
cell carcinoma formation”, comments Adriana Sánchez-Danés, the first author of the study.
In collaboration with Pr.Benjamin D Simons, Cavendish Laboratory and the Gurdon Institute,
University of Cambridge, UK, they developed a mathematical model of clonal evolution,
which defines for the first time, at the single cell resolution, the quantitative dynamics of
tumor initiation from the activation of the oncogene to the development of invasive tumours.
Interestingly, they found that oncogenic activation in progenitors lead to the generation of
pre-tumorigenic lesions that are frozen and cannot progress into invasive tumors. In contrast,
oncogene expression in stem cells resulted in a more rapid clonal expansion characterized
by an increase in self-renewing divisions combined with a higher resistance to cell death, and
leading in turn to the development of clones that progress into invasive tumors. These data
demonstrate that targeting stem cells, which reside at the top of the cellular hierarchy in the
skin epidermis, was necessary for tumor formation.
Altogether, this study provides important insights into the changes in the cellular dynamics
that lead to tumor formation and demonstrates that the capacity of oncogene expressing
cells to induce tumor formation depends on the specific clonal dynamics of the cancer cell of
origin. “This new finding not only demonstrates that the cancer cell of origin matters, but also
that stem cells are particularly sensitive to tumor initiation due to their natural ability to self-
renew and their resistance to oncogene mediated cell death. This mode of tumour
development suggests that therapy promoting differentiation or apoptosis should be effective
in the treatment of basal cell carcinomas, and should lead to tumour regression and prevent
tumour relapse.” explains Cédric Blanpain, the senior author of this Nature paper.
This work was supported by the FNRS, TELEVIE, a research grant from the Fondation
Contre le Cancer, the ULB fondation, Wellcome Trust and Trinity College Cambridge, the
foundation Bettencourt Schueller, the foundation Baillet Latour, the European Research
Council (ERC).
Journalists should credit Nature as the source of stories covered.
Adriana Sánchez-Danés*, Edouard Hannezo*, Jean-Christophe Larsimont, Mélanie Liagre, Khalil
Kass Youssef, Benjamin D Simons# and Cédric Blanpain#.
Defining the clonal dynamics leading to mouse skin tumour initiation
Nature, 2016. DOI 10.1038/nature19069
* denotes co-first authors # Corresponding authors
Contacts :
Cédric Blanpain, MD, PhD
Welbio, Interdisciplinary Research Institute (IRIBHM)
U-CRC, Université Libre de Bruxelles (ULB)
Tél. : [phone] ou 32-2- 555 4190
Email: [e-mail]
Lab Website: http://blanpainlab.ulb.ac.be/index.htm

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Benjamin D Simons, PhD
Herchel Smith Professor of Physics
Head of the Theory of Condensed Matter Physics Group
Cavendish Laboratory
Tel. [phone], Fax 337356, Admin. 746651
http://www.tcm.phy.cam.ac.uk/~bds10/
Email: [email protected]