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Cell Stem Cell. 2015 Jul 2;17(1):60-73. doi: 10.1016/j.stem.2015.05.008. Epub 2015 Jun 18.

Sox9 Controls Self-Renewal of Oncogene Targeted Cells and Links Tumor Initiation and Invasion.

Author information

1
Université Libre de Bruxelles, IRIBHM, Brussels 1070, Belgium.
2
Laboratory of Cancer Epigenetics, Faculty of Medicine, Université Libre de Bruxelles, Brussels 1070, Belgium.
3
EM-Facility EMoNe, VIB BIO Imaging Core, Center for Human Genetics Katholieke Universiteit Leuven, Leuven 3000, Belgium.
4
Laboratory for Molecular Cancer Biology, Center for the Biology of Disease, VIB, Leuven 3000, Belgium.
5
Inflammation Research Center, Image Core Facility, VIB, Ghent 9052, Belgium; VIB Bio Imaging Core, Ghent 9052, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent 9052, Belgium.
6
Department of Dermatology, Erasme Hospital, Université Libre de Bruxelles, Brussels 1070, Belgium.
7
Université Libre de Bruxelles, IRIBHM, Brussels 1070, Belgium; WELBIO, Université Libre de Bruxelles, Brussels 1070, Belgium. Electronic address: cedric.blanpain@ulb.ac.be.

Abstract

Sox9 is a transcription factor expressed in most solid tumors. However, the molecular mechanisms underlying Sox9 function during tumorigenesis remain unclear. Here, using a genetic mouse model of basal cell carcinoma (BCC), the most frequent cancer in humans, we show that Sox9 is expressed from the earliest step of tumor formation in a Wnt/β-catenin-dependent manner. Deletion of Sox9 together with the constitutive activation of Hedgehog signaling completely prevents BCC formation and leads to a progressive loss of oncogene-expressing cells. Transcriptional profiling of oncogene-expressing cells with Sox9 deletion, combined with in vivo ChIP sequencing, uncovers a cancer-specific gene network regulated by Sox9 that promotes stemness, extracellular matrix deposition, and cytoskeleton remodeling while repressing epidermal differentiation. Our study identifies the molecular mechanisms regulated by Sox9 that link tumor initiation and invasion.

PMID:
26095047
DOI:
10.1016/j.stem.2015.05.008
[Indexed for MEDLINE]
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