title: Focal adhesion kinase is required for β-catenin-induced mobilization of epidermal stem cells.
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.
authors.affiliation: The Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD,  UK.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Ridgway
authors.forename: Bryan
authors.initials: B
authors.lastname: Serrels
authors.forename: Susan
authors.initials: S
authors.lastname: Mason
authors.forename: Andrew
authors.initials: A
authors.lastname: Kinnaird
authors.forename: Morwenna
authors.initials: M
authors.lastname: Muir
authors.forename: Hitesh
authors.initials: H
authors.lastname: Patel
authors.forename: William J
authors.initials: WJ
authors.lastname: Muller
authors.forename: Owen J
authors.initials: OJ
authors.lastname: Sansom
authors.forename: Valerie G
authors.initials: VG
authors.lastname: Brunton
mesh_terms: D000818:Animals; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000502:physiology*; D018859:Hair Follicle / Q000166:cytology*; D019650:Hematopoietic Stem Cell Mobilization; D006965:Hyperplasia; D051379:Mice; D012878:Skin Neoplasms / Q000209:etiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D051176:beta Catenin / Q000502:physiology*; D019061:src-Family Kinases / Q000502:physiology
chemical_list: C495267:CTNNB1 protein, mouse; D051176:beta Catenin; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019061:src-Family Kinases; D013755:Tetradecanoylphorbol Acetate