Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenomatous Polyposis Coli Protein / metabolism
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Cadherins / metabolism
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Caveolin 1
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Caveolins / metabolism
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Cytoskeletal Proteins / genetics
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Cytoskeletal Proteins / metabolism*
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DNA-Binding Proteins / metabolism
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Epidermal Growth Factor / metabolism
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Glycogen Synthase Kinase 3 / metabolism
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Glycogen Synthase Kinase 3 beta
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Humans
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Lymphoid Enhancer-Binding Factor 1
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Neoplasms / genetics
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Neoplasms / metabolism*
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Proto-Oncogene Proteins / metabolism*
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Signal Transduction / physiology
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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Transcription Factors / metabolism
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Transcription, Genetic
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Transcriptional Activation*
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Wnt Proteins
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beta Catenin
Substances
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Adenomatous Polyposis Coli Protein
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CAV1 protein, human
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CTNNB1 protein, human
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Cadherins
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Caveolin 1
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Caveolins
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Cytoskeletal Proteins
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DNA-Binding Proteins
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Lymphoid Enhancer-Binding Factor 1
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Proto-Oncogene Proteins
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Trans-Activators
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Transcription Factors
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Wnt Proteins
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beta Catenin
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Epidermal Growth Factor
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GSK3B protein, human
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Glycogen Synthase Kinase 3 beta
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Glycogen Synthase Kinase 3