The RhoU/Wrch1 Rho GTPase gene is a common transcriptional target of both the gp130/STAT3 and Wnt-1 pathways

    Authors

    D. Schiavone; S. Dewilde; F. Vallania; J. Turkson; F. Di Cunto;V. Poli

    Comments

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    Abbreviated Journal Title

    Biochem. J.

    Keywords

    chromatin immunoprecipitation (ChIP); mouse embryonic fibroblast; promoter analysis; RhoU; signal transducer and activator of; transcription 3 (STAT3); Wnt-1; ACUTE-PHASE RESPONSE; UP-REGULATES STAT3; BETA-CATENIN; CONSTITUTIVE; ACTIVATION; INTERLEUKIN-6 RECEPTOR; SIGNAL-TRANSDUCTION; FACTOR-BINDING; FAMILY GTPASE; EXPRESSION; IDENTIFICATION; Biochemistry & Molecular Biology

    Abstract

    STAT3 (signal transducer and activator of transcription 3) is a transcription factor activated by cytokines, growth factors and oncogenes, whose activity is required for cell survival/proliferation of a wide variety of primary tumours and tumour cell lines. Prominent among its multiple effects on tumour cells is the stimulation of cell migration and metastasis, whose functional mechanisms are however not completely characterized. RhoU/Wrch 1 (Wnt-responsive Cdc42 homologue) is ail atypical Rho GTPase thought to be constitutively bound to GTP. RhoU was first identified as a Wnt-1-inducible mRNA and subsequently shown to act on the actin cytoskeleton by Stimulating filopodia formation and stress fibre dissolution. It was in addition recently shown to localize to focal adhesions and to Src-induced podosomes and enhance cell migration. RhoU overexpression in mammary epithelial Cells Stimulates quiescent cells to re-enter the cell cycle and morphologically phenocopies Wnt-1-dependent transformation. In the present Study we show that Writ-l-mediated RhoU induction occurs at the transcriptional level. Moreover, we demonstrate that RhoU can also be induced by gp130 cytokines via STAT3, and we identify two functional STAT3-binding sites oil the mouse RhoU promoter. RhoU induction by Wnt-1 is independent of beta-catenin, but does not involve STAT3. Rather, it is mediated by the Wnt/planar cell polarity pathway through the activation of JNK (c-Jun N-terminal kinase). Both the so-called non-canonical Wnt pathway and STAT3 are therefore able to induce RhoU, which in turn may be involved in mediating their effects oil cell migration.

    Journal Title

    Biochemical Journal

    Volume

    421

    Publication Date

    1-1-2009

    Document Type

    Article

    Language

    English

    First Page

    283

    Last Page

    292

    WOS Identifier

    WOS:000268088100015

    ISSN

    0264-6021

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