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beta-Catenin stabilizes the cadherin cell adhesion complex but, as a component of the Wnt/Wg signaling pathway, also controls gene expression by forming a heterodimer with a transcription factor of the LEF-TCF family. We demonstrate 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 fibronectin expression which was restored by activating the Wnt/Wg signaling cascade via LiCl treatment or transfection of either Xwnt-8 or beta-catenin. We isolated the Xenopus fibronectin gene (FN) promoter and found four putative LEF-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. LEF-1-related proteins were found in nuclei of the fibroblasts but were absent in a kidney epithelial cell line. Consistent with the lack of these transcription factors, the FN promoter was silent in the epithelial cells but was activated upon transfection of LEF-1. Wild-type Xenopus Tcf-3 (XTcf-3) was unable to activate FN promoter reporter constructs, while a mutant lacking 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. Brantjes, P. Moerer, M. van de Wetering, O. Destreé, 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 Wnt/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 adhesion.
Behrens,
Functional interaction of beta-catenin with the transcription factor LEF-1.
1996, Pubmed,
Xenbase
Behrens,
Functional interaction of beta-catenin with the transcription factor LEF-1.
1996,
Pubmed
,
Xenbase Bradley,
Expression of Wnt-1 in PC12 cells results in modulation of plakoglobin and E-cadherin and increased cellular adhesion.
1993,
Pubmed Brannon,
A beta-catenin/XTcf-3 complex binds to the siamois promoter to regulate dorsal axis specification in Xenopus.
1997,
Pubmed
,
Xenbase Cavallo,
Armadillo and dTCF: a marriage made in the nucleus.
1997,
Pubmed Chirgwin,
Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease.
1979,
Pubmed Danker,
V(+)-fibronectin expression and localization prior to gastrulation in Xenopus laevis embryos.
1993,
Pubmed
,
Xenbase Dean,
Cloning and analysis of the promotor region of the human fibronectin gene.
1987,
Pubmed DeSimone,
Identification and characterization of alternatively spliced fibronectin mRNAs expressed in early Xenopus embryos.
1992,
Pubmed
,
Xenbase Fagotto,
Cell contact-dependent signaling.
1996,
Pubmed Finnemann,
Cadherin transfection of Xenopus XTC cells downregulates expression of substrate adhesion molecules.
1995,
Pubmed
,
Xenbase Frixen,
E-cadherin-mediated cell-cell adhesion prevents invasiveness of human carcinoma cells.
1991,
Pubmed Giese,
The HMG domain of lymphoid enhancer factor 1 bends DNA and facilitates assembly of functional nucleoprotein structures.
1992,
Pubmed Grosschedl,
HMG domain proteins: architectural elements in the assembly of nucleoprotein structures.
1994,
Pubmed Gumbiner,
Signal transduction of beta-catenin.
1995,
Pubmed
,
Xenbase Gustafson,
Identification of multiple proteins that interact with functional regions of the human cardiac alpha-actin promoter.
1989,
Pubmed Hadeball,
Xenopus cadherin-11 (Xcadherin-11) expression requires the Wg/Wnt signal.
1998,
Pubmed
,
Xenbase He,
Identification of c-MYC as a target of the APC pathway.
1998,
Pubmed Heasman,
Overexpression of cadherins and underexpression of beta-catenin inhibit dorsal mesoderm induction in early Xenopus embryos.
1994,
Pubmed
,
Xenbase Hedgepeth,
Activation of the Wnt signaling pathway: a molecular mechanism for lithium action.
1997,
Pubmed
,
Xenbase Hinck,
Wnt-1 modulates cell-cell adhesion in mammalian cells by stabilizing beta-catenin binding to the cell adhesion protein cadherin.
1994,
Pubmed Hodivala,
Evidence that cadherins play a role in the downregulation of integrin expression that occurs during keratinocyte terminal differentiation.
1994,
Pubmed Hoffmann,
Cloning and expression analysis of a novel mesodermally expressed cadherin.
1995,
Pubmed Huber,
Nuclear localization of beta-catenin by interaction with transcription factor LEF-1.
1996,
Pubmed
,
Xenbase Ilyas,
Beta-catenin mutations in cell lines established from human colorectal cancers.
1997,
Pubmed Imagawa,
Transcription factor AP-2 mediates induction by two different signal-transduction pathways: protein kinase C and cAMP.
1987,
Pubmed Iwao,
Activation of the beta-catenin gene by interstitial deletions involving exon 3 in primary colorectal carcinomas without adenomatous polyposis coli mutations.
1998,
Pubmed Kemler,
From cadherins to catenins: cytoplasmic protein interactions and regulation of cell adhesion.
1993,
Pubmed Kimura,
Expression of cadherin-11 delineates boundaries, neuromeres, and nuclei in the developing mouse brain.
1996,
Pubmed Klein,
A molecular mechanism for the effect of lithium on development.
1996,
Pubmed
,
Xenbase Korinek,
Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma.
1997,
Pubmed Kühl,
Wnt signalling goes nuclear.
1997,
Pubmed
,
Xenbase Larabell,
Establishment of the dorso-ventral axis in Xenopus embryos is presaged by early asymmetries in beta-catenin that are modulated by the Wnt signaling pathway.
1997,
Pubmed
,
Xenbase Laurent,
The Xenopus homeobox gene twin mediates Wnt induction of goosecoid in establishment of Spemann's organizer.
1997,
Pubmed
,
Xenbase Lee,
Purified transcription factor AP-1 interacts with TPA-inducible enhancer elements.
1987,
Pubmed McKendry,
LEF-1/TCF proteins mediate wnt-inducible transcription from the Xenopus nodal-related 3 promoter.
1997,
Pubmed
,
Xenbase McNeill,
Novel function of the cell adhesion molecule uvomorulin as an inducer of cell surface polarity.
1990,
Pubmed Miyoshi,
Activation of the beta-catenin gene in primary hepatocellular carcinomas by somatic alterations involving exon 3.
1998,
Pubmed Molenaar,
XTcf-3 transcription factor mediates beta-catenin-induced axis formation in Xenopus embryos.
1996,
Pubmed
,
Xenbase Morin,
Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC.
1997,
Pubmed Munemitsu,
Regulation of intracellular beta-catenin levels by the adenomatous polyposis coli (APC) tumor-suppressor protein.
1995,
Pubmed Novak,
Cell adhesion and the integrin-linked kinase regulate the LEF-1 and beta-catenin signaling pathways.
1998,
Pubmed Patel,
Organization of the fibronectin gene provides evidence for exon shuffling during evolution.
1987,
Pubmed Perl,
A causal role for E-cadherin in the transition from adenoma to carcinoma.
1998,
Pubmed Reichmann,
Activation of an inducible c-FosER fusion protein causes loss of epithelial polarity and triggers epithelial-fibroblastoid cell conversion.
1992,
Pubmed Riese,
LEF-1, a nuclear factor coordinating signaling inputs from wingless and decapentaplegic.
1997,
Pubmed Roose,
The Xenopus Wnt effector XTcf-3 interacts with Groucho-related transcriptional repressors.
1998,
Pubmed
,
Xenbase Rubinfeld,
Stabilization of beta-catenin by genetic defects in melanoma cell lines.
1997,
Pubmed Schreiber,
Rapid detection of octamer binding proteins with 'mini-extracts', prepared from a small number of cells.
1989,
Pubmed Shackleford,
The Wnt-1 proto-oncogene induces changes in morphology, gene expression, and growth factor responsiveness in PC12 cells.
1993,
Pubmed Shimamura,
Wnt-1-dependent regulation of local E-cadherin and alpha N-catenin expression in the embryonic mouse brain.
1994,
Pubmed Slusarski,
Modulation of embryonic intracellular Ca2+ signaling by Wnt-5A.
1997,
Pubmed Sparks,
Mutational analysis of the APC/beta-catenin/Tcf pathway in colorectal cancer.
1998,
Pubmed Takeichi,
Morphogenetic roles of classic cadherins.
1995,
Pubmed Vleminckx,
Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor role.
1991,
Pubmed Young,
Wnt-1 induces growth, cytosolic beta-catenin, and Tcf/Lef transcriptional activation in Rat-1 fibroblasts.
1998,
Pubmed Zhu,
Expression of a dominant negative cadherin mutant inhibits proliferation and stimulates terminal differentiation of human epidermal keratinocytes.
1996,
Pubmed
