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Adult interfollicular tumour-initiating cells are reprogrammed into an embryonic hair follicle progenitor-like fate during basal cell carcinoma initiation
- Source :
- Nature Cell Biology. 14:1282-1294
- Publication Year :
- 2012
- Publisher :
- Springer Science and Business Media LLC, 2012.
-
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.
- Subjects :
- Keratinocytes
Cell signaling
Epidermis (botany)
Reverse Transcriptase Polymerase Chain Reaction
Wnt signaling pathway
Mice, Transgenic
Cell Biology
Biology
Flow Cytometry
Real-Time Polymerase Chain Reaction
medicine.disease
Immunohistochemistry
Cell biology
Mice
Carcinoma, Basal Cell
Neoplastic Stem Cells
medicine
Animals
Basal cell carcinoma
Progenitor cell
Smoothened
Hair Follicle
Reprogramming
Hedgehog
beta Catenin
Subjects
Details
- ISSN :
- 14764679 and 14657392
- Volume :
- 14
- Database :
- OpenAIRE
- Journal :
- Nature Cell Biology
- Accession number :
- edsair.doi.dedup.....4c2d7e328f78a036f1885131511329c6