title: 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.
authors.affiliation: Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Kristina
authors.initials: K
authors.lastname: Hertzler-Schaefer
authors.affiliation: Departments of Ophthalmology, Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
authors.forename: Grinu
authors.initials: G
authors.lastname: Mathew
authors.affiliation: Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Ally-Khan
authors.initials: AK
authors.lastname: Somani
authors.affiliation: Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Sunil
authors.initials: S
authors.lastname: Tholpady
authors.affiliation: Department of Biochemistry and Molecular Biology, Boonshoft School of Medicine, Wright State University, Dayton, OH 45435, USA.
authors.forename: Madhavi P
authors.initials: MP
authors.lastname: Kadakia
authors.affiliation: Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Dan F
authors.initials: DF
authors.lastname: Spandau
authors.affiliation: Departments of Ophthalmology, Pathology and Cell Biology, Columbia University, New York, NY 10032, USA. Electronic address: xz2369@columbia.edu.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D051526:Fibroblast Growth Factor 10 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D051059:PTEN Phosphohydrolase / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D014162:Transfection
chemical_list: C496463:FGF10 protein, human; C496464:Fgf10 protein, mouse; D051526:Fibroblast Growth Factor 10; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; C487757:Pten protein, mouse