Adult interfollicular tumour-initiating cells are reprogrammed into an embryonic hair follicle progenitor-like fate during basal cell carcinoma initiation - PubMed (original) (raw)

. 2012 Dec;14(12):1282-94.

doi: 10.1038/ncb2628. Epub 2012 Nov 25.

Gaëlle Lapouge, Karine Bouvrée, Sandrine Rorive, Sylvain Brohée, Ornella Appelstein, Jean-Christophe Larsimont, Vijayakumar Sukumaran, Bram Van de Sande, Doriana Pucci, Sophie Dekoninck, Jean-Valery Berthe, Stein Aerts, Isabelle Salmon, Véronique del Marmol, Cédric Blanpain

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Adult interfollicular tumour-initiating cells are reprogrammed into an embryonic hair follicle progenitor-like fate during basal cell carcinoma initiation

Khalil Kass Youssef et al. Nat Cell Biol. 2012 Dec.

Abstract

Basal cell carcinoma, the most frequent human skin cancer, arises from activating hedgehog (HH) pathway mutations; however, little is known about the temporal changes that occur in tumour-initiating cells from the first oncogenic hit to the development of invasive cancer. Using an inducible mouse model enabling the expression of a constitutively active Smoothened mutant (SmoM2) in the adult epidermis, we carried out transcriptional profiling of SmoM2-expressing cells at different times during cancer initiation. We found that tumour-initiating cells are massively reprogrammed into a fate resembling that of embryonic hair follicle progenitors (EHFPs). Wnt/ β-catenin signalling was very rapidly activated following SmoM2 expression in adult epidermis and coincided with the expression of EHFP markers. Deletion of β-catenin in adult SmoM2-expressing cells prevents EHFP reprogramming and tumour initiation. Finally, human basal cell carcinomas also express genes of the Wnt signalling and EHFP signatures.

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References

    1. J Cell Biol. 2011 Apr 4;193(1):235-50 - PubMed
    1. Nat Cell Biol. 2010 Mar;12(3):299-305 - PubMed
    1. Biostatistics. 2010 Apr;11(2):242-53 - PubMed
    1. Curr Biol. 1998 Sep 24;8(19):1058-68 - PubMed
    1. Br J Dermatol. 2009 Jun;160(6):1353-6 - PubMed

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