Conclusion
Pten loss in Lgr5+ cells induced Akt/β-catenin signaling, and SCCs can subsequently be raised as progeny from these primed Lgr5+ stem cells.
Methods
We established experiments with wildtype and Lgr5-CreER; Ptenflox/flox mice, and used DMBA/TPA two-stage skin carcinogenesis model to explore the effect of Pten loss in Lgr5+ HFSCs of 3 weeks old mice in skin carcinogenesis. In vitro experiments (cell culture and protein expression analysis) are employed to investigate molecular mechanisms involved.
Results
Pten loss in Lgr5+ HFSCs promoted SCC formation, which was attenuated in TNF-/- mice. Notably, β-catenin loss in Lgr5+ HFSCs decreased the formation of SCC. In addition, Pten loss in cultured epidermal stem cells upregulated the levels of both phospho-Akt and β-catenin.