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Science 296 (5573): 1644-1646

Copyright © 2002 by the American Association for the Advancement of Science

The Promise and Perils of Wnt Signaling Through beta -Catenin

Randall T. Moon,1* Bruce Bowerman,2 Michael Boutros,3 Norbert Perrimon3

Wnt pathways are involved in the control of gene expression, cell behavior, cell adhesion, and cell polarity. In addition, they often operate in combination with other signaling pathways. The Wnt/beta -catenin pathway is the best studied of the Wnt pathways and is highly conserved through evolution. In this pathway, Wnt signaling inhibits the degradation of beta -catenin, which can regulate transcription of a number of genes. Some of the genes regulated are those associated with cancer and other diseases (for example, colorectal cancer and melanomas). As a result, components of the Wnt/beta -catenin pathway are promising targets in the search for therapeutic agents. Information about Wnt pathways is available both in canonical terms and at the species level. In addition to the canonical Wnt/beta -catenin pathway, information is now available for Drosophila, Caenorhabditis elegans, and Xenopus. The STKE Connections Maps for these pathways provide an important tool in accessing this large body of complex information.

1 Howard Hughes Medical Institute, Department of Pharmacology, and Center for Developmental Biology, University of Washington School of Medicine, Seattle, WA 98195, USA.
2 Institute of Molecular Biology, University of Oregon, Eugene, OR 97403, USA.
3 Howard Hughes Medical Institute and Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
*   To whom correspondence should be addressed. E-mail: rtmoon{at}

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Wnt-7a Induces Presynaptic Colocalization of {alpha}7-Nicotinic Acetylcholine Receptors and Adenomatous Polyposis Coli in Hippocampal Neurons.
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J. Neurosci. 27, 5313-5325
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XTsh3 is an essential enhancing factor of canonical Wnt signaling in Xenopus axial determination.
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EMBO J. 26, 2350-2360
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Secreted frizzled related protein 2 (Sfrp2) is the key Akt-mesenchymal stem cell-released paracrine factor mediating myocardial survival and repair.
M. Mirotsou, Z. Zhang, A. Deb, L. Zhang, M. Gnecchi, N. Noiseux, H. Mu, A. Pachori, and V. Dzau (2007)
PNAS 104, 1643-1648
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Role for WNT16B in human epidermal keratinocyte proliferation and differentiation.
M.-T. Teh, D. Blaydon, L. R. Ghali, S. Edmunds, E. Pantazi, M. R. Barnes, I. M. Leigh, D. P. Kelsell, and M. P. Philpott (2007)
J. Cell Sci. 120, 330-339
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Patterning the zebrafish diencephalon by the conserved zinc-finger protein Fezl.
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Development 134, 127-136
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The making of Wnt: new insights into Wnt maturation, sorting and secretion.
D. Coudreuse and H. C. Korswagen (2007)
Development 134, 3-12
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Metastatic tumor antigen 3 is a direct corepressor of the Wnt4 pathway.
H. Zhang, R. R. Singh, A. H. Talukder, and R. Kumar (2006)
Genes & Dev. 20, 2943-2948
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Wnt/beta-Catenin Signaling Is a Normal Physiological Response to Mechanical Loading in Bone.
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Protein-tyrosine Phosphatase PCP-2 Inhibits beta-Catenin Signaling and Increases E-cadherin-dependent Cell Adhesion.
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J. Biol. Chem. 281, 15423-15433
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Nitric oxide-releasing aspirin and indomethacin are potent inhibitors against colon cancer in azoxymethane-treated rats: effects on molecular targets..
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Mol. Cancer Ther. 5, 1530-1538
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TC1(C8orf4) Correlates with Wnt/{beta}-Catenin Target Genes and Aggressive Biological Behavior in Gastric Cancer..
B. Kim, H. Koo, S. Yang, S. Bang, Y. Jung, Y. Kim, J. Kim, J. Park, R. T. Moon, K. Song, et al. (2006)
Clin. Cancer Res. 12, 3541-3548
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Nuclear trafficking of Drosophila Frizzled-2 during synapse development requires the PDZ protein dGRIP.
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PNAS 103, 7841-7846
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Mouse Cristin/R-spondin Family Proteins Are Novel Ligands for the Frizzled 8 and LRP6 Receptors and Activate beta-Catenin-dependent Gene Expression.
J.-S. Nam, T. J. Turcotte, P. F. Smith, S. Choi, and J. K. Yoon (2006)
J. Biol. Chem. 281, 13247-13257
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Negative Regulation of LRP6 Function by Casein Kinase I {epsilon} Phosphorylation.
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J. Biol. Chem. 281, 12233-12241
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Wnt3a gradient converts radial to bilateral feather symmetry via topological arrangement of epithelia.
Z. Yue, T.-X. Jiang, R. B. Widelitz, and C.-M. Chuong (2006)
PNAS 103, 951-955
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TC1 (C8orf4) Enhances the Wnt/{beta}-Catenin Pathway by Relieving Antagonistic Activity of Chibby.
Y. Jung, S. Bang, K. Choi, E. Kim, Y. Kim, J. Kim, J. Park, H. Koo, R. T. Moon, K. Song, et al. (2006)
Cancer Res. 66, 723-728
   Abstract »    Full Text »    PDF »
Wnt Proteins Prevent Apoptosis of Both Uncommitted Osteoblast Progenitors and Differentiated Osteoblasts by {beta}-Catenin-dependent and -independent Signaling Cascades Involving Src/ERK and Phosphatidylinositol 3-Kinase/AKT.
M. Almeida, L. Han, T. Bellido, S. C. Manolagas, and S. Kousteni (2005)
J. Biol. Chem. 280, 41342-41351
   Abstract »    Full Text »    PDF »
Adenovirus-Mediated Overexpression of REIC/Dkk-3 Selectively Induces Apoptosis in Human Prostate Cancer Cells through Activation of c-Jun-NH2-Kinase.
F. Abarzua, M. Sakaguchi, M. Takaishi, Y. Nasu, K. Kurose, S. Ebara, M. Miyazaki, M. Namba, H. Kumon, and N.-h. Huh (2005)
Cancer Res. 65, 9617-9622
   Abstract »    Full Text »    PDF »
Bcr is a negative regulator of the Wnt signalling pathway.
A. Ress and K. Moelling (2005)
EMBO Rep. 6, 1095-1100
   Abstract »    Full Text »    PDF »
Lithium rescues toxicity of aggregate-prone proteins in Drosophila by perturbing Wnt pathway.
Z. Berger, E. K. Ttofi, C. H. Michel, M. Y. Pasco, S. Tenant, D. C. Rubinsztein, and C. J. O'Kane (2005)
Hum. Mol. Genet. 14, 3003-3011
   Abstract »    Full Text »    PDF »
Wnt/{beta}-catenin signaling activates growth-control genes during overload-induced skeletal muscle hypertrophy.
D. D. Armstrong and K. A. Esser (2005)
Am J Physiol Cell Physiol 289, C853-C859
   Abstract »    Full Text »    PDF »
On mammary stem cells.
W. A. Woodward, M. S. Chen, F. Behbod, and J. M. Rosen (2005)
J. Cell Sci. 118, 3585-3594
   Abstract »    Full Text »    PDF »
Wnt signalling mediated by Tbx2b regulates cell migration during formation of the neural plate.
S. H. Fong, A. Emelyanov, C. Teh, and V. Korzh (2005)
Development 132, 3587-3596
   Abstract »    Full Text »    PDF »
Stomatal Patterning and Differentiation by Synergistic Interactions of Receptor Kinases.
E. D. Shpak, J. M. McAbee, L. J. Pillitteri, and K. U. Torii (2005)
Science 309, 290-293
   Abstract »    Full Text »    PDF »
Regulating Inducible Transcription Through Controlled Localization.
E. C. Ziegler and S. Ghosh (2005)
Sci. STKE 2005, re6
   Abstract »    Full Text »    PDF »
Functional Genomic Analysis of the Wnt-Wingless Signaling Pathway.
R. DasGupta, A. Kaykas, R. T. Moon, and N. Perrimon (2005)
Science 308, 826-833
   Abstract »    Full Text »    PDF »
Cell adhesion and signal transduction in cancer: Conference on Cadherins, Catenins and Cancer.
W. Birchmeier (2005)
EMBO Rep. 6, 413-417
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The Mechanism of Endogenous Receptor Activation Functionally Distinguishes Prototype Canonical and Noncanonical Wnts.
G. Liu, A. Bafico, and S. A. Aaronson (2005)
Mol. Cell. Biol. 25, 3475-3482
   Abstract »    Full Text »    PDF »
Expression of secreted Wnt antagonists in gastrointestinal tissues: potential role in stem cell homeostasis.
T Byun, M Karimi, J L Marsh, T Milovanovic, F Lin, and R F Holcombe (2005)
J. Clin. Pathol. 58, 515-519
   Abstract »    Full Text »    PDF »
Casein Kinase 2- and Protein Kinase A-regulated Adenomatous Polyposis Coli and {beta}-Catenin Cellular Localization Is Dependent on p38 MAPK.
J. Hildesheim, J. M. Salvador, M. C. Hollander, and A. J. Fornace Jr. (2005)
J. Biol. Chem. 280, 17221-17226
   Abstract »    Full Text »    PDF »
G protein-coupled lysophosphatidic acid receptors stimulate proliferation of colon cancer cells through the {beta}-catenin pathway.
M. Yang, W. W. Zhong, N. Srivastava, A. Slavin, J. Yang, T. Hoey, and S. An (2005)
PNAS 102, 6027-6032
   Abstract »    Full Text »    PDF »
Role that phosphorylation of GSK3 plays in insulin and Wnt signalling defined by knockin analysis.
E. J. McManus, K. Sakamoto, L. J. Armit, L. Ronaldson, N. Shpiro, R. Marquez, and D. R. Alessi (2005)
EMBO J. 24, 1571-1583
   Abstract »    Full Text »    PDF »
The role of Axin2 in calvarial morphogenesis and craniosynostosis.
H.-M. I. Yu, B. Jerchow, T.-J. Sheu, B. Liu, F. Costantini, J. E. Puzas, W. Birchmeier, and W. Hsu (2005)
Development 132, 1995-2005
   Abstract »    Full Text »    PDF »

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