RGD Reference Report - Pten loss induces autocrine FGF signaling to promote skin tumorigenesis. - Rat Genome Database

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Pten loss induces autocrine FGF signaling to promote skin tumorigenesis.

Authors: Hertzler-Schaefer, Kristina  Mathew, Grinu  Somani, Ally-Khan  Tholpady, Sunil  Kadakia, Madhavi P  Chen, Yiping  Spandau, Dan F  Zhang, Xin 
Citation: Hertzler-Schaefer K, etal., Cell Rep. 2014 Mar 13;6(5):818-26. doi: 10.1016/j.celrep.2014.01.045. Epub 2014 Feb 27.
RGD ID: 126928134
Pubmed: PMID:24582960   (View Abstract at PubMed)
PMCID: PMC4080841   (View Article at PubMed Central)
DOI: DOI:10.1016/j.celrep.2014.01.045   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
FGF10Humanskin papilloma  ISOFgf10 (Mus musculus)protein:increased expression:skin (mouse)RGD 
Fgf10Ratskin papilloma  ISOFgf10 (Mus musculus)protein:increased expression:skin (mouse)RGD 
Fgf10Mouseskin papilloma  IEP protein:increased expression:skin (mouse)RGD 
FGF10Humanskin squamous cell carcinoma  ISOFgf10 (Mus musculus)Pten conditional KO mouseRGD 
Fgf10Ratskin squamous cell carcinoma  ISOFgf10 (Mus musculus)Pten conditional KO mouseRGD 
Fgf10Mouseskin squamous cell carcinoma  IEP protein:increased expression:skin (mouse)RGD 
Fgf10Mouseskin squamous cell carcinoma  IMP Pten conditional KO mouseRGD 
PTENHumanskin squamous cell carcinoma amelioratesISOPten (Mus musculus) RGD 
PtenRatskin squamous cell carcinoma amelioratesISOPten (Mus musculus) RGD 
PtenMouseskin squamous cell carcinoma amelioratesIGIRGD:1556939|RGD:1323418 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Fgf10  (fibroblast growth factor 10)
Pten  (phosphatase and tensin homolog)

Genes (Mus musculus)
Fgf10  (fibroblast growth factor 10)
Pten  (phosphatase and tensin homolog)

Genes (Homo sapiens)
FGF10  (fibroblast growth factor 10)
PTEN  (phosphatase and tensin homolog)


Additional Information