Cadherins and Catenins: Role in Signal Transduction and Tumor Progression

Cadherins are transmembrane cell–cell adhesion molecules which are connected to the cytoskeleton by association with the cytoplasmic proteins, α-, β-, and γ-catenin (plakoglobin). β-catenin has an additional role in the wnt signal transduction pathway in which it transmitts signals to the cell nucleus in complexes with transcription factors of the LEF-1/TCF family. The cell adhesion function of the epithelial E-cadherin is frequently disturbed in carcinomas either by downregulation or by mutation of the E-cadherin/catenin genes. The signaling function of β-catenin is activated in tumors by mutations of β-catenin or of the tumor suppressor gene product APC. In this review I will give an introduction to the structure and function of the cadherin/catenin complex and summarize findings which support a decisive role of these components in the development of cancer.

[1]  M. Takeichi,et al.  Cadherin cell adhesion receptors as a morphogenetic regulator. , 1991, Science.

[2]  J. Lilien,et al.  The Nonreceptor Protein Tyrosine Phosphatase PTP1B Binds to the Cytoplasmic Domain of N-Cadherin and Regulates the Cadherin–Actin Linkage , 1998, The Journal of cell biology.

[3]  W. Birchmeier,et al.  Functional interaction of an axin homolog, conductin, with beta-catenin, APC, and GSK3beta. , 1998, Science.

[4]  S. Dedhar,et al.  Cell adhesion and the integrin-linked kinase regulate the LEF-1 and beta-catenin signaling pathways. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[5]  G. Struhl,et al.  Regulation of the Hedgehog and Wingless signalling pathways by the F-box/WD40-repeat protein Slimb , 1998, Nature.

[6]  R. Hynes,et al.  Developmental defects in mouse embryos lacking N-cadherin. , 1997, Developmental biology.

[7]  Y. Marikawa,et al.  β-TrCP is a negative regulator of the Wnt/β-catenin signaling pathway and dorsal axis formation in Xenopus embryos , 1998, Mechanisms of Development.

[8]  Paul Polakis,et al.  Downregulation of β-catenin by human Axin and its association with the APC tumor suppressor, β-catenin and GSK3β , 1998, Current Biology.

[9]  M. Buendia,et al.  Somatic mutations of the beta-catenin gene are frequent in mouse and human hepatocellular carcinomas. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[10]  J. Gordon,et al.  Inflammatory Bowel Disease and Adenomas in Mice Expressing a Dominant Negative N-Cadherin , 1995, Science.

[11]  K. Mostov,et al.  Dynamics of β-Catenin Interactions with APC Protein Regulate Epithelial Tubulogenesis , 1997, The Journal of cell biology.

[12]  W. Fiers,et al.  Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor role , 1991, Cell.

[13]  M. Mareel,et al.  The E-cadherin/catenin complex in invasion and metastasis. , 1996, Current topics in microbiology and immunology.

[14]  Konrad Basler,et al.  pangolinencodes a Lef-1 homologue that acts downstream of Armadillo to transduce the Wingless signal in Drosophila , 1997, Nature.

[15]  R. Moon,et al.  A beta-catenin/XTcf-3 complex binds to the siamois promoter to regulate dorsal axis specification in Xenopus. , 1997, Genes & development.

[16]  F. Lottspeich,et al.  The uvomorulin-anchorage protein alpha catenin is a vinculin homologue. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[17]  P. Soballe,et al.  Mutations in beta-catenin are uncommon in colorectal cancer occurring in occasional replication error-positive tumors. , 1997, Cancer research.

[18]  C. Raffel,et al.  Sporadic Medulloblastomas Contain Oncogenic β-Catenin Mutations , 1998 .

[19]  Peter D. Kwong,et al.  Structural basis of cell-cell adhesion by cadherins , 1995, Nature.

[20]  W. Birchmeier,et al.  Dissociation of Madin-Darby canine kidney epithelial cells by the monoclonal antibody anti-arc-1: mechanistic aspects and identification of the antigen as a component related to uvomorulin , 1985, The Journal of cell biology.

[21]  Bert Vogelstein,et al.  Mutational Analysis of the APC/β-Catenin/Tcf Pathway in Colorectal Cancer , 1998 .

[22]  E. Gelmann,et al.  β-Catenin Mutations in Human Prostate Cancer , 1998 .

[23]  D. R. Coman Decreased Mutual Adhesiveness, a Property of Cells from Squamous Cell Carcinomas , 1944 .

[24]  C. Muchardt,et al.  RB and c-Myc Activate Expression of the E-Cadherin Gene in Epithelial Cells through Interaction with Transcription Factor AP-2 , 1998, Molecular and Cellular Biology.

[25]  Hans Clevers,et al.  Depletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4 , 1998, Nature Genetics.

[26]  H. Höfler,et al.  No evidence for mutations in the alpha- and beta-catenin genes in human gastric and breast carcinomas. , 1996, Cancer research.

[27]  T. Yoneda,et al.  E-cadherin expression in human breast cancer cells suppresses the development of osteolytic bone metastases in an experimental metastasis model. , 1996, Cancer research.

[28]  Hans Clevers,et al.  Drosophila Tcf and Groucho interact to repress Wingless signalling activity , 1998, Nature.

[29]  P. Lipponen,et al.  Expression of E‐cadherin (E‐CD) as related to other prognostic factors and survival in breast cancer , 1994, The Journal of pathology.

[30]  Mariann Bienz,et al.  LEF-1, a Nuclear Factor Coordinating Signaling Inputs from wingless and decapentaplegic , 1997, Cell.

[31]  T. Dale,et al.  Signal transduction by the Wnt family of ligands. , 1998, The Biochemical journal.

[32]  Y. Nakamura,et al.  Activation of the beta-catenin gene by interstitial deletions involving exon 3 in primary colorectal carcinomas without adenomatous polyposis coli mutations. , 1998, Cancer research.

[33]  A. Sparks,et al.  Identification of c-MYC as a target of the APC pathway. , 1998, Science.

[34]  Heinz Höfler,et al.  Mutations of the human E‐cadherin (CDH1) gene , 1998, Human mutation.

[35]  W. Birchmeier,et al.  Targeted mutation of plakoglobin in mice reveals essential functions of desmosomes in the embryonic heart , 1996, The Journal of cell biology.

[36]  L. Larue,et al.  E-cadherin null mutant embryos fail to form a trophectoderm epithelium. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[37]  A. Harris,et al.  Wnt5a cloning, expression, and up-regulation in human primary breast cancers. , 1995, Clinical cancer research : an official journal of the American Association for Cancer Research.

[38]  W. Birchmeier,et al.  E-cadherin expression in squamous cell carcinomas of head and neck: inverse correlation with tumor dedifferentiation and lymph node metastasis. , 1991, Cancer research.

[39]  J. Nathans,et al.  A Member of the Frizzled Protein Family Mediating Axis Induction by Wnt-5A , 1997, Science.

[40]  A. Bauer,et al.  Pontin52, an interaction partner of beta-catenin, binds to the TATA box binding protein. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[41]  S. Butz,et al.  An a-E-catenin gene trap mutation defines its function in preimplantation development ( cell adhesion y blastocyst y epithelial cells ) , 1997 .

[42]  M. Takeichi,et al.  The 102 kd cadherin-associated protein: Similarity to vinculin and posttranscriptional regulation of expression , 1991, Cell.

[43]  L. Larue,et al.  Lack of beta-catenin affects mouse development at gastrulation. , 1995, Development.

[44]  H. Höfler,et al.  E-cadherin gene mutations provide clues to diffuse type gastric carcinomas. , 1994, Cancer research.

[45]  W. Birchmeier,et al.  Expression of E-cadherin and catenins in invasive mammary carcinomas. , 1997, Anticancer research.

[46]  K. Kinzler,et al.  Lessons from Hereditary Colorectal Cancer , 1996, Cell.

[47]  John G. Collard,et al.  Inhibition of invasion of epithelial cells by Tiam1-Rac signaling. , 1997, Science.

[48]  W. Birchmeier,et al.  Prognostic value of E‐cadherin expression in 413 gastric carcinomas , 1996, International journal of cancer.

[49]  D. Cox,et al.  Mode of proviral activation of a putative mammary oncogene (int-1) on mouse chromosome 15 , 1984, Nature.

[50]  Michael Kühl,et al.  Functional interaction of β-catenin with the transcription factor LEF-1 , 1996, Nature.

[51]  Akira Kikuchi,et al.  Axil, a Member of the Axin Family, Interacts with Both Glycogen Synthase Kinase 3β and β-Catenin and Inhibits Axis Formation ofXenopus Embryos , 1998, Molecular and Cellular Biology.

[52]  Akira Kikuchi,et al.  Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK‐3β and β‐catenin and promotes GSK‐3β‐dependent phosphorylation of β‐catenin , 1998 .

[53]  B. Herrmann,et al.  Nuclear localization of β-catenin by interaction with transcription factor LEF-1 , 1996, Mechanisms of Development.

[54]  T. Sugimura,et al.  Beta-catenin is frequently mutated and demonstrates altered cellular location in azoxymethane-induced rat colon tumors. , 1998, Cancer research.

[55]  E. Fuchs,et al.  Lymphoid enhancer factor 1 directs hair follicle patterning and epithelial cell fate. , 1995, Genes & development.

[56]  M. Takeichi Morphogenetic roles of classic cadherins. , 1995, Current opinion in cell biology.

[57]  Stephen W. Byers,et al.  Serine Phosphorylation-regulated Ubiquitination and Degradation of β-Catenin* , 1997, The Journal of Biological Chemistry.

[58]  Shintaro T. Suzuki Structural and functional diversity of cadherin superfamily: Are new members of cadherin superfamily involved in signal transduction pathway? , 1996, Journal of cellular biochemistry.

[59]  Sven Berg,et al.  A repeating amino acid motif shared by proteins with diverse cellular roles , 1994, Cell.

[60]  E. Fuchs,et al.  De Novo Hair Follicle Morphogenesis and Hair Tumors in Mice Expressing a Truncated β-Catenin in Skin , 1998, Cell.

[61]  M. Bienz TCF: transcriptional activator or repressor? , 1998, Current opinion in cell biology.

[62]  Mariann Bienz,et al.  Drosophila CBP represses the transcription factor TCF to antagonize Wingless signalling , 1998, Nature.

[63]  M. Ringwald,et al.  Uvomorulin-catenin complex formation is regulated by a specific domain in the cytoplasmic region of the cell adhesion molecule. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[64]  J. Gordon,et al.  In vivo analysis of cadherin function in the mouse intestinal epithelium: essential roles in adhesion, maintenance of differentiation, and regulation of programmed cell death , 1995, The Journal of cell biology.

[65]  T. Uemura,et al.  α-Catenin-Vinculin Interaction Functions to Organize the Apical Junctional Complex in Epithelial Cells , 1998, The Journal of cell biology.

[66]  R. Nusse,et al.  Wnt signaling: a common theme in animal development. , 1997, Genes & development.

[67]  B. Gumbiner,et al.  Nuclear localization signal-independent and importin/karyopherin-independent nuclear import of β-catenin , 1998, Current Biology.

[68]  E. Wieschaus,et al.  Regulation of Armadillo by a Drosophila APC Inhibits Neuronal Apoptosis during Retinal Development , 1998, Cell.

[69]  R. Hynes,et al.  Contact and adhesive specificities in the associations, migrations, and targeting of cells and axons , 1992, Cell.

[70]  M. Takeichi,et al.  Cadherins: a molecular family important in selective cell-cell adhesion. , 1990, Annual review of biochemistry.

[71]  Y. Nakamura,et al.  Activation of the beta-catenin gene in primary hepatocellular carcinomas by somatic alterations involving exon 3. , 1998, Cancer research.

[72]  L. Chodosh,et al.  Precocious Mammary Gland Development in P-Cadherin–deficient Mice , 1997, The Journal of cell biology.

[73]  J. Daniel,et al.  Tyrosine phosphorylation and cadherin/catenin function , 1997, BioEssays : news and reviews in molecular, cellular and developmental biology.

[74]  Jeremy Nathans,et al.  A new member of the frizzled family from Drosophila functions as a Wingless receptor , 1996, Nature.

[75]  D. Riethmacher,et al.  A targeted mutation in the mouse E-cadherin gene results in defective preimplantation development. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[76]  D. Kufe,et al.  Interaction of the DF3/MUC1 Breast Carcinoma-associated Antigen and β-Catenin in Cell Adhesion* , 1997, The Journal of Biological Chemistry.

[77]  I. Nimmrich,et al.  A β‐catenin mutation in a sporadic colorectal tumor of the RER phenotype and absence of β‐catenin germline mutations in FAP patients , 1998, Genes, chromosomes & cancer.

[78]  B. Obrink,et al.  Cell-cell contacts mediated by E-cadherin (uvomorulin) restrict invasive behavior of L-cells , 1991, The Journal of cell biology.

[79]  D. M. Ferkey,et al.  GBP, an Inhibitor of GSK-3, Is Implicated in Xenopus Development and Oncogenesis , 1998, Cell.

[80]  S. Sokol,et al.  Axis determination in Xenopus involves biochemical interactions of axin, glycogen synthase kinase 3 and β-catenin , 1998, Current Biology.

[81]  W. Birchmeier,et al.  Immunohistological analysis of E-cadherin, α-, β- and γ-catenin expression in colorectal cancer: implications for cell adhesion and signaling , 1999 .

[82]  P. Polakis The adenomatous polyposis coli (APC) tumor suppressor. , 1997, Biochimica et biophysica acta.

[83]  Paul Polakis,et al.  Binding of GSK3β to the APC-β-Catenin Complex and Regulation of Complex Assembly , 1996, Science.

[84]  J. Gordon,et al.  Forced expression of E-cadherin in the mouse intestinal epithelium slows cell migration and provides evidence for nonautonomous regulation of cell fate in a self-renewing system. , 1996, Genes & development.

[85]  Hans Clevers,et al.  Activation of β-Catenin-Tcf Signaling in Colon Cancer by Mutations in β-Catenin or APC , 1997, Science.

[86]  A. Takashima,et al.  Direct association of presenilin‐1 with β‐catenin , 1998 .

[87]  Frans,et al.  Loss of epithelial differentiation and gain of invasiveness correlates with tyrosine phosphorylation of the E-cadherin/beta-catenin complex in cells transformed with a temperature-sensitive v-SRC gene , 1993, The Journal of cell biology.

[88]  H. Kotani,et al.  Regulation of Cell–Cell Adhesion by Rac and Rho Small G Proteins in MDCK Cells , 1997, The Journal of cell biology.

[89]  S. Hirohashi,et al.  Beta-catenin mutation in carcinoma of the uterine endometrium. , 1998, Cancer research.

[90]  Jörg Stappert,et al.  β‐catenin is a target for the ubiquitin–proteasome pathway , 1997 .

[91]  Benjamin Geiger,et al.  Differential Nuclear Translocation and Transactivation Potential of β-Catenin and Plakoglobin , 1998, The Journal of cell biology.

[92]  Akinao Nose,et al.  Expressed recombinant cadherins mediate cell sorting in model systems , 1988, Cell.

[93]  S. Hirohashi,et al.  Silencing of the E-cadherin invasion-suppressor gene by CpG methylation in human carcinomas. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[94]  I. El-Hariry,et al.  Expression of E-cadherin-associated molecules (alpha-, beta-, and gamma-catenins and p120) in colorectal polyps. , 1997, The American journal of pathology.

[95]  B. Jockusch,et al.  Vinculin Is Part of the Cadherin–Catenin Junctional Complex: Complex Formation between α-Catenin and Vinculin , 1998, The Journal of cell biology.

[96]  W. Birchmeier,et al.  E-cadherin-mediated cell-cell adhesion prevents invasiveness of human carcinoma cells , 1991, The Journal of cell biology.

[97]  Hideki Yamamoto,et al.  Axin, a Negative Regulator of the Wnt Signaling Pathway, Directly Interacts with Adenomatous Polyposis Coli and Regulates the Stabilization of β-Catenin* , 1998, The Journal of Biological Chemistry.

[98]  S. Hirohashi Inactivation of the E-cadherin-mediated cell adhesion system in human cancers. , 1998, The American journal of pathology.

[99]  David I. Smith,et al.  Identification and Chromosomal Localization of CTNNAL1, a Novel Protein Homologous to α-Catenin , 1998 .

[100]  J. Gordon,et al.  Effects of Forced Expression of an NH2-terminal Truncated β-Catenin on Mouse Intestinal Epithelial Homeostasis , 1998, The Journal of cell biology.

[101]  A. Brown,et al.  Transformation by Wnt family proteins correlates with regulation of beta-catenin. , 1997, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[102]  S. Hirohashi,et al.  Dominant negative inhibition of the association between beta-catenin and c-erbB-2 by N-terminally deleted beta-catenin suppresses the invasion and metastasis of cancer cells. , 1996, Oncogene.

[103]  Mitsuhiko Ikura,et al.  Structural basis of calcium-induced E-cadherin rigidification and dimerization , 1996 .

[104]  R. Moon,et al.  The axis-inducing activity, stability, and subcellular distribution of beta-catenin is regulated in Xenopus embryos by glycogen synthase kinase 3. , 1996, Genes & development.

[105]  L. Larue,et al.  Lack of beta-catenin affects mouse development at gastrulation. , 1995, Development.

[106]  Carien M. Niessen,et al.  The Juxtamembrane Region of the Cadherin Cytoplasmic Tail Supports Lateral Clustering, Adhesive Strengthening, and Interaction with p120ctn , 1998, The Journal of cell biology.

[107]  H Clevers,et al.  TCF/LEF factor earn their wings. , 1997, Trends in genetics : TIG.

[108]  T. Sugimura,et al.  High frequency of beta-catenin (ctnnb1) mutations in the colon tumors induced by two heterocyclic amines in the F344 rat. , 1998, Cancer research.

[109]  A. Hall,et al.  The Small GTPases Rho and Rac Are Required for the Establishment of Cadherin-dependent Cell–Cell Contacts , 1997, The Journal of cell biology.

[110]  M. Vijver,et al.  E‐cadherin is a tumour/invasion suppressor gene mutated in human lobular breast cancers. , 1995, The EMBO journal.

[111]  W. Birchmeier,et al.  Cadherin expression in carcinomas: role in the formation of cell junctions and the prevention of invasiveness. , 1994, Biochimica et biophysica acta.

[112]  Hans Clevers,et al.  XTcf-3 Transcription Factor Mediates β-Catenin-Induced Axis Formation in Xenopus Embryos , 1996, Cell.

[113]  Anthony E. Reeve,et al.  E-cadherin germline mutations in familial gastric cancer , 1998, Nature.

[114]  S. Hirohashi,et al.  Identification of a neural α-catenin as a key regulator of cadherin function and multicellular organization , 1992, Cell.

[115]  H. Höfler,et al.  No Evidence for Mutations in the α- and β-Catenin Genes in Human Gastric and Breast Carcinomas , 1996 .

[116]  Paul Polakis,et al.  Stabilization of β-Catenin by Genetic Defects in Melanoma Cell Lines , 1997, Science.

[117]  P. Polakis,et al.  Deletion of an amino-terminal sequence beta-catenin in vivo and promotes hyperphosporylation of the adenomatous polyposis coli tumor suppressor protein , 1996, Molecular and cellular biology.

[118]  M. Takeichi,et al.  Cell binding function of E‐cadherin is regulated by the cytoplasmic domain. , 1988, The EMBO journal.

[119]  W. Birchmeier,et al.  Mechanisms Identified in the Transcriptional Control of Epithelial Gene Expression (*) , 1996, The Journal of Biological Chemistry.

[120]  P. McCrea,et al.  beta-Catenin associates with the actin-bundling protein fascin in a noncadherin complex , 1996, The Journal of cell biology.

[121]  R Kemler,et al.  Embryonic heart and skin defects in mice lacking plakoglobin. , 1996, Developmental biology.

[122]  J. Palacios,et al.  Mutations in the β-Catenin Gene (CTNNB1) in Endometrioid Ovarian Carcinomas , 1998 .

[123]  W. Birchmeier,et al.  E-cadherin and APC compete for the interaction with beta-catenin and the cytoskeleton , 1994, The Journal of cell biology.

[124]  Wei Hsu,et al.  The Mouse Fused Locus Encodes Axin, an Inhibitor of the Wnt Signaling Pathway That Regulates Embryonic Axis Formation , 1997, Cell.

[125]  Robert S. Kerbel,et al.  E-Cadherin–dependent Growth Suppression is Mediated by the Cyclin-dependent Kinase Inhibitor p27KIP1 , 1998, The Journal of cell biology.

[126]  B. Gumbiner,et al.  Cell Adhesion: The Molecular Basis of Tissue Architecture and Morphogenesis , 1996, Cell.

[127]  H. Shiozaki,et al.  Expression of e-cadherin and alpha-catenin molecules in human breast-cancer tissues and association with clinicopathological features. , 1994, International journal of oncology.

[128]  J. Cleveland,et al.  p120, a novel substrate of protein tyrosine kinase receptors and of p60v-src, is related to cadherin-binding factors beta-catenin, plakoglobin and armadillo. , 1992, Oncogene.

[129]  J. Herman,et al.  E-cadherin expression is silenced by DNA hypermethylation in human breast and prostate carcinomas. , 1995, Cancer research.

[130]  N. Nomura,et al.  Role of IQGAP1, a target of the small GTPases Cdc42 and Rac1, in regulation of E-cadherin- mediated cell-cell adhesion. , 1998, Science.

[131]  Robert Kay,et al.  Expression cloning of oncogenes by retroviral transfer of cDNA libraries , 1995, Molecular and cellular biology.

[132]  W. Birchmeier,et al.  Role of morphogenetic factors in metastasis of mammary carcinoma cells , 1998, Oncogene.

[133]  I Fariñas,et al.  Development of several organs that require inductive epithelial-mesenchymal interactions is impaired in LEF-1-deficient mice. , 1994, Genes & development.

[134]  P. Stein,et al.  Tyrosine Phosphorylation and Src Family Kinases Control Keratinocyte Cell–Cell Adhesion , 1998, The Journal of cell biology.

[135]  W. Birchmeier,et al.  Progression of carcinoma cells is associated with alterations in chromatin structure and factor binding at the E-cadherin promoter in vivo. , 1995, Oncogene.

[136]  K. Kinzler,et al.  Constitutive Transcriptional Activation by a β-Catenin-Tcf Complex in APC−/− Colon Carcinoma , 1997, Science.

[137]  M. Peifer,et al.  Wingless signaling: The inconvenient complexities of life , 1998, Current Biology.

[138]  William I. Weis,et al.  Three-Dimensional Structure of the Armadillo Repeat Region of β-Catenin , 1997, Cell.

[139]  S. Aaronson,et al.  Characterization of Wnt-1 and Wnt-2 induced growth alterations and signaling pathways in NIH3T3 fibroblasts , 1998, Oncogene.

[140]  Gerhard Christofori,et al.  A causal role for E-cadherin in the transition from adenoma to carcinoma , 1998, Nature.

[141]  Hans Clevers,et al.  The Xenopus Wnt effector XTcf-3 interacts with Groucho-related transcriptional repressors , 1998, Nature.

[142]  W. Birchmeier,et al.  The E-cadherin promoter: functional analysis of a G.C-rich region and an epithelial cell-specific palindromic regulatory element. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[143]  M. Tyers,et al.  Combinatorial control in ubiquitin-dependent proteolysis: don't Skp the F-box hypothesis. , 1998, Trends in genetics : TIG.

[144]  R. Grosschedl,et al.  LEF-1/TCF proteins mediate wnt-inducible transcription from the Xenopus nodal-related 3 promoter. , 1997, Developmental biology.

[145]  W. Birchmeier,et al.  Dissecting tumor cell invasion: epithelial cells acquire invasive properties after the loss of uvomorulin-mediated cell-cell adhesion , 1989, The Journal of cell biology.

[146]  M. Mann,et al.  Identification of the receptor component of the IκBα–ubiquitin ligase , 1998, Nature.

[147]  Walter Birchmeier,et al.  Hot papers in cell biology - J. Behrens, J.P. von Kries, M. Kuehl, L. Bruhn, D. Wedlich, R. Grosschedl, W. Birchmeier: "Functional interaction of beta-catenin with the transcription factor LEF-1" - Comments by Walter Birchmeier , 1999 .