Pten loss induces autocrine FGF signaling to promote skin tumorigenesis.

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 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.

journal_name

Cell Rep

journal_title

Cell reports

authors

Hertzler-Schaefer K,Mathew G,Somani AK,Tholpady S,Kadakia MP,Chen Y,Spandau DF,Zhang X

doi

10.1016/j.celrep.2014.01.045

subject

Has Abstract

pub_date

2014-03-13 00:00:00

pages

818-26

issue

5

issn

2211-1247

pii

S2211-1247(14)00079-5

journal_volume

6

pub_type

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