Title

The Rhou/Wrch1 Rho Gtpase Gene Is A Common Transcriptional Target Of Both The Gp130/Stat3 And Wnt-1 Pathways

Keywords

Chromatin immunoprecipitation (ChIP); Mouse embryonic fibroblast; Promoter analysis; RhoU; Signal transducer and activator of transcription 3 (STAT3); Wnt-1

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/Wrch1 (Wnt-responsive Cdc42 homologue) is an atypical Rho GTPase thought to be constitutively bound to GTP. RhoU was first identified as a Wnt-1-induciblemRNAand 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 Wnt-1-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 on the mouse RhoU promoter. RhoU induction by Wnt-1 is independent of β-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 socalled non-canonical Wnt pathway and STAT3 are therefore able to induce RhoU, which in turn may be involved in mediating their effects on cell migration. © The Authors Journal compilation.

Publication Date

7-15-2009

Publication Title

Biochemical Journal

Volume

421

Issue

2

Number of Pages

283-292

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1042/BJ20090061

Socpus ID

67650908700 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/67650908700

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