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 Spandau, Xin Zhang

Research output: Contribution to journalArticle

18 Citations (Scopus)

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
Pages (from-to)818-826
Number of pages9
JournalCell Reports
Volume6
Issue number5
DOIs
StatePublished - 2014

Fingerprint

Autocrine Communication
Skin
Carcinogenesis
Tumors
Chemical activation
Transcription
Neoplasms
Phosphatidylinositol 3-Kinases
Papilloma
Squamous Cell Carcinoma
Proteins

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Hertzler-Schaefer, K., Mathew, G., Somani, A-K., Tholpady, S., Kadakia, M. P., Chen, Y., ... 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

Pten loss induces autocrine FGF signaling to promote skin tumorigenesis. / Hertzler-Schaefer, Kristina; Mathew, Grinu; Somani, Ally-Khan; Tholpady, Sunil; Kadakia, Madhavi P.; Chen, Yiping; Spandau, Dan; Zhang, Xin.

In: Cell Reports, Vol. 6, No. 5, 2014, p. 818-826.

Research output: Contribution to journalArticle

Hertzler-Schaefer, K, Mathew, G, Somani, A-K, Tholpady, S, Kadakia, MP, Chen, Y, Spandau, D & Zhang, X 2014, 'Pten loss induces autocrine FGF signaling to promote skin tumorigenesis', Cell Reports, vol. 6, no. 5, pp. 818-826. https://doi.org/10.1016/j.celrep.2014.01.045
Hertzler-Schaefer, Kristina ; Mathew, Grinu ; Somani, Ally-Khan ; Tholpady, Sunil ; Kadakia, Madhavi P. ; Chen, Yiping ; Spandau, Dan ; Zhang, Xin. / Pten loss induces autocrine FGF signaling to promote skin tumorigenesis. In: Cell Reports. 2014 ; Vol. 6, No. 5. pp. 818-826.
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