Wnt signaling: physiology and pathology.
Signaling by the Wnt family of secreted glycoproteins has been demonstrated to be essential both in normal embryonic development and in the pathogenesis of a variety of diseases, including cancer. This signaling pathway is exquisitely regulated by a large and complex array of proteins, which act as agonists or antagonists of signal transduction, modulating the Wnt signal extracellularly, in the cytoplasm and in the nucleus. Here, we will briefly review the canonical Wnt signaling pathway and consider molecular defects in Wnt signaling components known to promote uncontrolled cell growth following induction of Wnt signaling. We will also focus on two recently identified factors in this pathway, that seem to act as Wnt signaling antagonists, one functioning in the cytoplasm called Disabled-2 and the other in the nucleus named Chibby.
Prunier
Céline
C
Department of Cell Biology, NC1, Cleveland Clinic Lerner College of Medicine, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Hocevar
Barbara A
BA
Howe
Philip H
PH
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D060466:Axin Protein; D002352:Carrier Proteins / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D003593:Cytoplasm / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D047108:Embryonic Development; D016147:Genes, Tumor Suppressor; D006023:Glycoproteins / Q000737:chemistry*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D025521:Tumor Suppressor Proteins; D051153:Wnt Proteins; D051176:beta Catenin
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D051017:Apoptosis Regulatory Proteins; D060466:Axin Protein; C473750:CBY1 protein, human; C495270:CTNNB1 protein, human; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C102885:DAB2 protein, human; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins; D051153:Wnt Proteins; D051176:beta Catenin; D004247:DNA