| Autor: |
Youssef KK; IRIBHM, Université Libre de Bruxelles (ULB), 808 route de Lennik, 1070 Brussels, Belgium., Lapouge G, Bouvrée K, Rorive S, Brohée S, Appelstein O, Larsimont JC, Sukumaran V, Van de Sande B, Pucci D, Dekoninck S, Berthe JV, Aerts S, Salmon I, del Marmol V, Blanpain C |
| Jazyk: |
angličtina |
| Zdroj: |
Nature cell biology [Nat Cell Biol] 2012 Dec; Vol. 14 (12), pp. 1282-94. Date of Electronic Publication: 2012 Nov 25. |
| DOI: |
10.1038/ncb2628 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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