The Wnt/Wg signal transducer beta-catenin controls fibronectin expression

beta-Catenin stabilizes the cadherin cell adhesion complex but, as a compon ent of the Wnt/Wg signaling pathway, also controls gene expression by formi ng a heterodimer with a transcription factor of the LEF-TCF family. We demo nstrate that the substrate adhesion molecule fibronectin is a direct target of Wnt/Wg signaling. Nuclear depletion of beta-catenin following cadherin transfection in Xenopus fibroblasts resulted in downregulation of fibronect in expression which was restored by activating the Wnt/Wg signaling cascade via LiCl treatment or transfection of either Xwnt-8 or beta-catenin. We is olated the Xenopus fibronectin gene (FN) promoter and found four putative L EF-TCF binding sites. By comparing the activities of different fibronectin gene reporter constructs in fibroblasts and cadherin transfectants, the LEF -TCF site at position -368: was identified as a Wnt/Wg response element. LE F-1-related proteins were found in nuclei of the fibroblasts but were absen t in a kidney epithelial cell line. Consistent with the lack of these trans cription factors, the FN promoter was silent in the epithelial cells but wa s activated upon transfection of LEF-1. Wild-type Xenopus Tcf-3 (XTcf-3) wa s unable to activate FN promoter reporter constructs, while a mutant lackin g the groucho binding region behaved like LEF-1. In contrast to XTcf-3, LEF -1 does not interact with groucho proteins, which turn TCFs into activators or repressors (J. Roose, M. Molenaar, J. Hurenkamp, J. Peterson, H, Brantj es, P. Moerer, M. van de Wetering, O. Destree, and H. Clevers, Nature; 395: 608-612, 1998). Together these: data provide evidence that expressing LEF-1 enables fibroblasts, in contrast to epithelial cells, to respond to the Wn t/Wg signal via beta-catenin in stimulating fibronectin gene transcription. . Our findings further promote the idea that due to its dual function, beta -catenin regulates the balance between cell-cell and cell-substrate adhesio n.