title: Adult interfollicular tumour-initiating cells are reprogrammed into an embryonic hair follicle progenitor-like fate during basal cell carcinoma initiation.
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.
authors.affiliation: IRIBHM, Université Libre de Bruxelles (ULB), 808 route de Lennik, 1070 Brussels, Belgium.
authors.forename: Khalil Kass
authors.initials: KK
authors.lastname: Youssef
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Lapouge
authors.forename: Karine
authors.initials: K
authors.lastname: Bouvrée
authors.forename: Sandrine
authors.initials: S
authors.lastname: Rorive
authors.forename: Sylvain
authors.initials: S
authors.lastname: Brohée
authors.forename: Ornella
authors.initials: O
authors.lastname: Appelstein
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Larsimont
authors.forename: Vijayakumar
authors.initials: V
authors.lastname: Sukumaran
authors.forename: Bram
authors.initials: B
authors.lastname: Van de Sande
authors.forename: Doriana
authors.initials: D
authors.lastname: Pucci
authors.forename: Sophie
authors.initials: S
authors.lastname: Dekoninck
authors.forename: Jean-Valery
authors.initials: JV
authors.lastname: Berthe
authors.forename: Stein
authors.initials: S
authors.lastname: Aerts
authors.forename: Isabelle
authors.initials: I
authors.lastname: Salmon
authors.forename: Véronique
authors.initials: V
authors.lastname: del Marmol
authors.forename: Cédric
authors.initials: C
authors.lastname: Blanpain
mesh_terms: D000818:Animals; D002280:Basal Cell Carcinoma / Q000378:metabolism / Q000473:pathology*; D005434:Flow Cytometry; D018859:Hair Follicle / Q000166:cytology* / Q000378:metabolism; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D014411:Neoplastic Stem Cells / Q000166:cytology* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051176:beta Catenin / Q000378:metabolism
chemical_list: D051176:beta Catenin