Year: 2016
Type: article
Abstract: Deficiency in PTEN (phosphatase and tensin homolog deleted on chromosome 10) is the underlying cause of PTEN hamartoma tumor syndrome and a wide variety of human cancers. In skin epidermis, we have previously identified an autocrine FGF signaling induced by loss of Pten in keratinocytes. In this study, we demonstrate that skin hyperplasia requires FGF receptor adaptor protein Frs2α and tyrosine phosphatase Shp2, two upstream regulators of Ras signaling. Although the PI3-kinase regulatory subunits p85α and p85β are dispensable, the PI3-kinase catalytic subunit p110α requires interaction with Ras to promote hyperplasia in Pten-deficient skin, thus demonstrating an important cross-talk between Ras and PI3K pathways. Furthermore, genetic and pharmacological inhibition of Ras-MAPK pathway impeded epidermal hyperplasia in Pten animals. These results reveal a positive feedback loop connecting Pten and Ras pathways and suggest that FGF-activated Ras-MAPK pathway is an effective therapeutic target for preventing skin tumor induced by aberrant Pten signaling.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
Awards: Columbia University Medical Center Skin Disease Research Center (CUMCSDRC), Core Facilities for Vision Research, Molecular and cellular communications in liver tumorigenesis, Lens ectoderm-derived Wnt signaling regulates eye development, G4026490766, Shp2 and Pten in Leukemia and Anemia, G4343165571, Targeting the p110beta Isoform of PI3 Kinase in Pten Null Tumors, G5303268458, Dissection of Pten-regulated signals in hepatopathogenesis, G6824552465, G7054731815, B-RAF drives regenerative axon growth in the optic nerve in vivo, G8591520557, Integrating biomechanical and biochemical signaling in lacrimal gland development, Signaling Mechanisms of Lens Development
OpenAlex ID: W2542609257