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Mol Cell Biol
1999 Aug 01;198:5576-87. doi: 10.1128/MCB.19.8.5576.
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The Wnt/Wg signal transducer beta-catenin controls fibronectin expression.
Gradl D
,
Kühl M
,
Wedlich D
.
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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
DeSimone,
Identification and characterization of alternatively spliced fibronectin mRNAs expressed in early Xenopus embryos.
1992,
Pubmed
,
Xenbase
Dean,
Cloning and analysis of the promotor region of the human fibronectin gene.
1987,
Pubmed
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
