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Title

Cutaneous cancer stem cell maintenance is dependent on β-catenin signalling

AuthorsPeinado, Héctor; Cano, Amparo ; Huelsken, Joerg
Issue Date2008
PublisherNature Publishing Group
CitationNature 452(7187): 650-653 (2008)
AbstractContinuous 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 β-catenin signalling as being essential in sustaining the CSC phenotype. Ablation of the β-catenin gene results in the loss of CSCs and complete tumour regression. In addition, we provide evidence for the involvement of increased β-catenin signalling in malignant human squamous cell carcinomas. Because Wnt/β-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. ©2008 Nature Publishing Group.
URIhttp://hdl.handle.net/10261/82184
DOI10.1038/nature06835
Identifiersdoi: 10.1038/nature06835
issn: 0028-0836
e-issn: 1476-4687
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