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

par Kass, Youssef Khalil ;Lapouge, Gaëlle ;Bouvree, Karine ;Rorive, Sandrine ;Brohée, Sylvain ;Appelstein, Ornella ;Larsimont, Jean-Christophe ;Sukumaran, Vijayakumar ;Van de Sande, Bram;Pucci, Doriana ;Dekoninck, Sophie ;Berthe, Jean-Valéry ;Aerts, Stein;Salmon, Isabelle ;Del Marmol, Véronique ;Blanpain, Cédric
Référence Nature cell biology, 14, page (1282-1294)
Publication Publié, 2012-11

Article révisé par les pairs

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Résumé :

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.