Abstract：
:Epidermal integrity is a complex process established during embryogenesis and maintained throughout the organism lifespan by epithelial stem cells. Although Wnt regulates normal epithelial stem cell renewal, aberrant Wnt signaling can contribute to cancerous growth. Here, we explored the consequences of persistent expressing Wnt1 in an epidermal compartment that includes the epithelial stem cells. Surprisingly, Wnt caused the rapid growth of the hair follicles, but this was followed by epithelial cell senescence, disappearance of the epidermal stem cell compartment, and progressive hair loss. Although Wnt1 induced the activation of beta-catenin and the mTOR pathway, both hair follicle hyperproliferation and stem cell exhaustion were strictly dependent on mTOR function. These findings suggest that whereas activation of beta-catenin contributes to tumor growth, epithelial stem cells may be endowed with a protective mechanism that results in cell senescence upon the persistent stimulation of proliferative pathways that activate mTOR, ultimately suppressing tumor formation.
journal_name
Cell Stem Celljournal_title
Cell stem cellauthors
Castilho RM,Squarize CH,Chodosh LA,Williams BO,Gutkind JSdoi
10.1016/j.stem.2009.06.017subject
Has Abstractpub_date
2009-09-04 00:00:00pages
279-89issue
3eissn
1934-5909issn
1875-9777pii
S1934-5909(09)00301-4journal_volume
5pub_type
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