Targeting of Ras-mediated FGF signaling suppresses Pten-deficient skin tumor Academic Article uri icon

Overview

MeSH Major

  • MAP Kinase Signaling System
  • Mitogen-Activated Protein Kinase 1
  • Neural Crest

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.

publication date

  • November 15, 2016

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC5135310

Digital Object Identifier (DOI)

  • 10.1073/pnas.1604450113

PubMed ID

  • 27799550

Additional Document Info

start page

  • 13156

end page

  • 13161

volume

  • 113

number

  • 46