Pten Loss Induces Autocrine FGF Signaling to Promote Skin Tumorigenesis
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 acti...
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| Format: | Article |
| Language: | English |
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Elsevier
2014-03-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124714000795 |
| _version_ | 1819240710315966464 |
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| author | Kristina Hertzler-Schaefer Grinu Mathew Ally-Khan Somani Sunil Tholpady Madhavi P. Kadakia Yiping Chen Dan F. Spandau Xin Zhang |
| author_facet | Kristina Hertzler-Schaefer Grinu Mathew Ally-Khan Somani Sunil Tholpady Madhavi P. Kadakia Yiping Chen Dan F. Spandau Xin Zhang |
| author_sort | Kristina Hertzler-Schaefer |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-23T14:12:20Z |
| format | Article |
| id | doaj.art-ba469c189cb9470e81ae9d4479c0b9d7 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-23T14:12:20Z |
| publishDate | 2014-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-ba469c189cb9470e81ae9d4479c0b9d72022-12-21T17:44:01ZengElsevierCell Reports2211-12472014-03-016581882610.1016/j.celrep.2014.01.045Pten Loss Induces Autocrine FGF Signaling to Promote Skin TumorigenesisKristina Hertzler-Schaefer0Grinu Mathew1Ally-Khan Somani2Sunil Tholpady3Madhavi P. Kadakia4Yiping Chen5Dan F. Spandau6Xin Zhang7Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599, USADepartments of Ophthalmology, Pathology and Cell Biology, Columbia University, New York, NY 10032, USADepartment of Dermatology, Indiana University School of Medicine, Indianapolis, IN 46202, USADepartment of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USADepartment of Biochemistry and Molecular Biology, Boonshoft School of Medicine, Wright State University, Dayton, OH 45435, USADepartment of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USADepartment of Dermatology, Indiana University School of Medicine, Indianapolis, IN 46202, USADepartments of Ophthalmology, Pathology and Cell Biology, Columbia University, New York, NY 10032, USAInactivation 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.http://www.sciencedirect.com/science/article/pii/S2211124714000795 |
| spellingShingle | Kristina Hertzler-Schaefer Grinu Mathew Ally-Khan Somani Sunil Tholpady Madhavi P. Kadakia Yiping Chen Dan F. Spandau Xin Zhang Pten Loss Induces Autocrine FGF Signaling to Promote Skin Tumorigenesis Cell Reports |
| title | Pten Loss Induces Autocrine FGF Signaling to Promote Skin Tumorigenesis |
| title_full | Pten Loss Induces Autocrine FGF Signaling to Promote Skin Tumorigenesis |
| title_fullStr | Pten Loss Induces Autocrine FGF Signaling to Promote Skin Tumorigenesis |
| title_full_unstemmed | Pten Loss Induces Autocrine FGF Signaling to Promote Skin Tumorigenesis |
| title_short | Pten Loss Induces Autocrine FGF Signaling to Promote Skin Tumorigenesis |
| title_sort | pten loss induces autocrine fgf signaling to promote skin tumorigenesis |
| url | http://www.sciencedirect.com/science/article/pii/S2211124714000795 |
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