학술논문
Adult interfollicular tumour-initiating cells are reprogrammed into an embryonic hair follicle progenitor-like fate during basal cell carcinoma initiation.
Document Type
Article
Author
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
Source
Subject
*TUMORS
*HAIR follicles
*EMBRYOS
*BASAL cell carcinoma
*SKIN cancer
*PROGENITOR cells
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Language
ISSN
1465-7392
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/ ?-catenin signalling was very rapidly activated following SmoM2 expression in adult epidermis and coincided with the expression of EHFP markers. Deletion of ?-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. [ABSTRACT FROM AUTHOR]