Wnt-independent beta-catenin transactivation in tumor development.
Accumulation of beta-catenin, which leads to enhanced TCF/LEF-1 driven transcription and thereby contributes to tumor development, can result from mutation of beta-catenin itself, inactivation of the adenomatous polyposis coli (APC) protein, or Wnt pathway inhibition of the GSK-3beta kinase that together with APC promotes beta-catenin degradation. Nevertheless, emerging evidence shows that the activation of beta-catenin can occur independently of Wnt signaling to GSK-3beta. In response to EGF, tumor cells overexpressing EGF receptor display GSK-3beta-independent activation of beta-catenin, which may result from a combination of effects-EGF-stimulated, caveolin-1-dependent internalization of E-cadherin, resulting in release of beta-catenin from cell-cell contacts, and EGF-induced downregulation of caveolin-1, relieving the inhibition of signaling molecules sequestered by caveolin-1 at caveolae.
Lu
Zhimin
Z
University of Texas M.D. Anderson Cancer Center, Department of Neuro-Oncology, Houston 77030, USA. zhiminlu@mdanderson.org
Hunter
Tony
T
D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D051242:Caveolin 1; D022461:Caveolins / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D051821:Lymphoid Enhancer-Binding Factor 1; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D051153:Wnt Proteins; D051176:beta Catenin
D025601:Adenomatous Polyposis Coli Protein; C495540:CAV1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D051242:Caveolin 1; D022461:Caveolins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D051821:Lymphoid Enhancer-Binding Factor 1; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin; D004815:Epidermal Growth Factor; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3