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Title: Adult interfollicular tumour-initiating cells are reprogrammed into an embryonic hair follicle progenitor-like fate during basal cell carcinoma initiation
Authors: Youssef, Khalil Kass ×
Lapouge, Gaëlle
Bouvrée, Karine
Rorive, Sandrine
Brohée, Sylvain
Appelstein, Ornella
Larsimont, Jean-Christophe
Sukumaran, Vijayakumar
Van de Sande, Bram
Pucci, Doriana
Dekoninck, Sophie
Berthe, Jean-Valery
Aerts, Stein
Salmon, Isabelle
Del Marmol, Véronique
Blanpain, Cédric #
Issue Date: Dec-2012
Publisher: Macmillan Magazines Ltd.
Series Title: Nature Cell Biology vol:14 issue:12 pages:1282-1294
Article number: 10.1038/ncb2628
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.
URI: 
ISSN: 1465-7392
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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