Pten loss induces autocrine FGF signaling to promote skin tumorigenesis

Kristina Hertzler-Schaefer, Grinu Mathew, Ally Khan Somani, Sunil Tholpady, Madhavi P. Kadakia, Yiping Chen, Dan F. Spandau, Xin Zhang

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Inactivation 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 invitro and invivo. 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.

Original languageEnglish (US)
Pages (from-to)818-826
Number of pages9
JournalCell Reports
Volume6
Issue number5
DOIs
StatePublished - Jan 1 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Hertzler-Schaefer, K., Mathew, G., Somani, A. K., Tholpady, S., Kadakia, M. P., Chen, Y., Spandau, D. F., & Zhang, X. (2014). Pten loss induces autocrine FGF signaling to promote skin tumorigenesis. Cell Reports, 6(5), 818-826. https://doi.org/10.1016/j.celrep.2014.01.045