title: Sox9 Controls Self-Renewal of Oncogene Targeted Cells and Links Tumor Initiation and Invasion.
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.
authors.affiliation: Université Libre de Bruxelles, IRIBHM, Brussels 1070, Belgium.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Larsimont
authors.affiliation: Université Libre de Bruxelles, IRIBHM, Brussels 1070, Belgium.
authors.forename: Khalil Kass
authors.initials: KK
authors.lastname: Youssef
authors.affiliation: Université Libre de Bruxelles, IRIBHM, Brussels 1070, Belgium.
authors.forename: Adriana
authors.initials: A
authors.lastname: Sánchez-Danés
authors.affiliation: Université Libre de Bruxelles, IRIBHM, Brussels 1070, Belgium.
authors.forename: Vijayakumar
authors.initials: V
authors.lastname: Sukumaran
authors.affiliation: Laboratory of Cancer Epigenetics, Faculty of Medicine, Université Libre de Bruxelles, Brussels 1070, Belgium.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Defrance
authors.affiliation: Laboratory of Cancer Epigenetics, Faculty of Medicine, Université Libre de Bruxelles, Brussels 1070, Belgium.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Delatte
authors.affiliation: Université Libre de Bruxelles, IRIBHM, Brussels 1070, Belgium.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Liagre
authors.affiliation: EM-Facility EMoNe, VIB BIO Imaging Core, Center for Human Genetics Katholieke Universiteit Leuven, Leuven 3000, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Baatsen
authors.affiliation: Laboratory for Molecular Cancer Biology, Center for the Biology of Disease, VIB, Leuven 3000, Belgium.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Marine
authors.affiliation: 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.
authors.forename: Saskia
authors.initials: S
authors.lastname: Lippens
authors.affiliation: 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.
authors.forename: Christopher
authors.initials: C
authors.lastname: Guerin
authors.affiliation: Department of Dermatology, Erasme Hospital, Université Libre de Bruxelles, Brussels 1070, Belgium.
authors.forename: Véronique
authors.initials: V
authors.lastname: Del Marmol
authors.affiliation: Université Libre de Bruxelles, IRIBHM, Brussels 1070, Belgium.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Vanderwinden
authors.affiliation: Laboratory of Cancer Epigenetics, Faculty of Medicine, Université Libre de Bruxelles, Brussels 1070, Belgium.
authors.forename: Francois
authors.initials: F
authors.lastname: Fuks
authors.affiliation: Université Libre de Bruxelles, IRIBHM, Brussels 1070, Belgium; WELBIO, Université Libre de Bruxelles, Brussels 1070, Belgium. Electronic address: cedric.blanpain@ulb.ac.be.
authors.forename: Cédric
authors.initials: C
authors.lastname: Blanpain
mesh_terms: D008841:Actin Cytoskeleton / Q000502:physiology; D000818:Animals; D063646:Carcinogenesis; D002280:Basal Cell Carcinoma / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D002448:Cell Adhesion; D000066673:Cell Self Renewal / Q000235:genetics / Q000502:physiology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D005109:Extracellular Matrix / Q000502:physiology; D005260:Female; D017353:Gene Deletion; D053823:Hedgehog Proteins / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008954:Models, Biological; D009154:Mutation; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000502:physiology*; D009857:Oncogenes; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000502:physiology; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D000072086:Smoothened Receptor
chemical_list: D053823:Hedgehog Proteins; D043562:Receptors, G-Protein-Coupled; D055758:SOX9 Transcription Factor; C491022:Smo protein, mouse; D000072086:Smoothened Receptor; C527933:Sox9 protein, mouse