title: Epidermal growth factor receptor/beta-catenin/T-cell factor 4/matrix metalloproteinase 1: a new pathway for regulating keratinocyte invasiveness after UVA irradiation.
abstract: Previous studies have established that UV irradiation results in epidermal growth factor receptor (EGFR) activation in keratinocytes. However, the signaling pathways and cellular effects related to this process remain incompletely elucidated. Herein, we describe for the first time that UVA-mediated EGFR activation results in beta-catenin tyrosine phosphorylation at the Y654 residue responsible for the dissociation of E-cadherin/alpha-catenin/beta-catenin complexes. Moreover, UVA induces an EGFR-dependent, but Wnt-independent, beta-catenin relocalization from the membrane to the nucleus followed by its association with T-cell factor 4 (TCF4). This newly formed beta-catenin/TCF4 complex binds to a specific site on matrix metalloproteinase 1 (MMP1) promoter and governs MMP1 gene and protein expression, as well as cell migration in collagen and gelatin. Altogether, these results suggest that UVA stimulates keratinocyte invasiveness through two coordinated EGFR-dependent processes: loss of cell-to-cell contact due to beta-catenin/E-cadherin/alpha-catenin dissociation and increased cell migration through extracellular matrix component degradation due to beta-catenin/TCF4-dependent MMP1 regulation. These events may represent an important step in epidermis repair following UVA injury and their abnormal regulation could contribute to photoaging and photocarcinogenesis.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U563, Toulouse cedex-3, France. christine.jean@inserm.fr
authors.forename: Christine
authors.initials: C
authors.lastname: Jean
authors.forename: Amandine
authors.initials: A
authors.lastname: Blanc
authors.forename: Naïs
authors.initials: N
authors.lastname: Prade-Houdellier
authors.forename: Loïc
authors.initials: L
authors.lastname: Ysebaert
authors.forename: Hélène
authors.initials: H
authors.lastname: Hernandez-Pigeon
authors.forename: Talal
authors.initials: T
authors.lastname: Al Saati
authors.forename: Marie-José
authors.initials: MJ
authors.lastname: Haure
authors.forename: Addolorata-Maria-Luce
authors.initials: AM
authors.lastname: Coluccia
authors.forename: Marie
authors.initials: M
authors.lastname: Charveron
authors.forename: Eric
authors.initials: E
authors.lastname: Delabesse
authors.forename: Guy
authors.initials: G
authors.lastname: Laurent