Catenins, Wnt signaling and cancer.
Recent studies indicate that plakoglobin may have a similar function to that of beta-catenin within the Wnt signaling pathway. beta-catenin is known to be an oncogene in many forms of human cancer, following acquisition of stabilizing mutations in amino terminal sequences. Kolligs(1) and coworkers show, however, that unlike beta-catenin, plakoglobin induces neoplastic transformation of rat epithelial cells in the absence of such stabilizing mutations. Cellular transformation by plakoglobin also appears to be distinct from that of beta-catenin in that it requires activation of the proto-oncogene c-myc. Surprisingly, c-myc is activated more efficiently by plakoglobin than beta-catenin, despite its previous identification as a target of Tcf/beta-catenin.(2) In contrast, a synthetic Tcf reporter gene is activated to a much greater extent by beta-catenin than plakoglobin. Plakoglobin and beta-catenin may therefore have different roles in Wnt signaling and cancer, which reflect their differential effects on target gene activity.
Barker
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University Medical Center Utrecht, Department of Immunology, The Netherlands. Nbarker@lab.azu.nl
Clevers
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H
D000818:Animals; D003598:Cytoskeletal Proteins / Q000378:metabolism* / Q000502:physiology; D051180:Desmoplakins; D009369:Neoplasms / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; D051185:gamma Catenin
D003598:Cytoskeletal Proteins; D051180:Desmoplakins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; D051185:gamma Catenin