Focal adhesion kinase is required for β-catenin-induced mobilization of epidermal stem cells

Rachel A. Ridgway, Bryan Serrels, Susan Mason, Andrew Kinnaird, Morwenna Muir, Hitesh Patel, William J. Muller, Owen J. Sansom, Valerie G. Brunton*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that integrates signals downstream of integrin and growth factor activation. Previously, we have shown that skin-specific loss of fak prevents chemically induced skin carcinogenesis in mice following phorbol ester treatment. In this study, we show that skin-specific deletion of fak prevents mobilization of stem cells within the bulge region of the hair follicle, which are the precursors of papillomas following phorbol ester treatment. We also show that phorbol ester treatment results in activation of-catenin within the skin and that FAK is required for β-catenin-induced stem cell mobilization. In addition, inhibition of Src kinase activity, a major binding partner of FAK also prevents stem cell mobilization. We show that FAK is required for the nuclear localization of β-catenin in the skin following phorbol ester treatment and the transcriptional activation of the β-catenin target gene c-Myc. This provides the first evidence of cross-talk between integrin and Wnt signalling pathways in the control of epidermal stem cells and the early events associated with skin carcinogenesis.
Original languageEnglish
Pages (from-to)2369-2376
Number of pages8
JournalCarcinogenesis
Volume33
Issue number12
DOIs
Publication statusPublished - Dec 2012

Keywords

  • TUMOR-FORMATION
  • TRANSIENT ACTIVATION
  • MOUSE EPIDERMIS
  • HAIR FOLLICLE MORPHOGENESIS
  • LABEL-RETAINING CELLS
  • SKIN CARCINOGENESIS
  • C-SRC
  • CANCER-CELLS
  • MUTANT MICE
  • EPITHELIAL-SPECIFIC DISRUPTION

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