title: Cutaneous cancer stem cell maintenance is dependent on beta-catenin signalling.
abstract: Continuous turnover of epithelia is ensured by the extensive self-renewal capacity of tissue-specific stem cells. Similarly, epithelial tumour maintenance relies on cancer stem cells (CSCs), which co-opt stem cell properties. For most tumours, the cellular origin of these CSCs and regulatory pathways essential for sustaining stemness have not been identified. In murine skin, follicular morphogenesis is driven by bulge stem cells that specifically express CD34. Here we identify a population of cells in early epidermal tumours characterized by phenotypic and functional similarities to normal bulge skin stem cells. This population contains CSCs, which are the only cells with tumour initiation properties. Transplants derived from these CSCs preserve the hierarchical organization of the primary tumour. We describe beta-catenin signalling as being essential in sustaining the CSC phenotype. Ablation of the beta-catenin gene results in the loss of CSCs and complete tumour regression. In addition, we provide evidence for the involvement of increased beta-catenin signalling in malignant human squamous cell carcinomas. Because Wnt/beta-catenin signalling is not essential for normal epidermal homeostasis, such a mechanistic difference may thus be targeted to eliminate CSCs and consequently eradicate squamous cell carcinomas.
authors.affiliation: Ecole Polytechnique Fédérale de Lausanne/ISREC (Swiss Institute for Experimental Cancer Research) and National Center of Competence in Research Molecular Oncology, Chemin des Boveresses 155, 1066 Epalinges, Switzerland.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Malanchi
authors.forename: Hector
authors.initials: H
authors.lastname: Peinado
authors.forename: Deepika
authors.initials: D
authors.lastname: Kassen
authors.forename: Thomas
authors.initials: T
authors.lastname: Hussenet
authors.forename: Daniel
authors.initials: D
authors.lastname: Metzger
authors.forename: Pierre
authors.initials: P
authors.lastname: Chambon
authors.forename: Marcel
authors.initials: M
authors.lastname: Huber
authors.forename: Daniel
authors.initials: D
authors.lastname: Hohl
authors.forename: Amparo
authors.initials: A
authors.lastname: Cano
authors.forename: Walter
authors.initials: W
authors.lastname: Birchmeier
authors.forename: Joerg
authors.initials: J
authors.lastname: Huelsken
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D004817:Epidermis / Q000473:pathology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000473:pathology*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D018952:Antigens, CD34; D051176:beta Catenin