Pten Loss Induces Autocrine FGF Signaling to Promote Skin Tumorigenesis

• Pten deletion induces Fgf10 expression in skin epidermis
• Fgf10 is regulated at the translational level by mTORC1
• Overexpression of Fgf10 reproduces skin papillomas
• PTEN deficiency in human cutaneous SCC correlates with higher FGF10 levels

SummaryInactivation of the Pten tumor suppressor negatively regulates the PI3K-mTOR pathway. In a model of cutaneous squamous cell carcinoma (SCC), we demonstrate that deletion of Pten strongly elevates Fgf10 protein levels without increasing Fgf10 transcription in vitro and in vivo. The translational activation of Fgf10 by Pten deletion is reversed by genetic disruption of the mTORC1 complex, which also prevents skin tumorigenesis in Pten mutants. We further show that ectopic expression of Fgf10 causes skin papillomas, whereas Pten deletion-induced skin tumors are inhibited by epidermal deletion of Fgfr2. Collectively, our data identify autocrine activation of FGF signaling as an essential mechanism in promoting Pten-deficient skin tumors.

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