Catenins, Wnt signaling and cancer

Recent studies indicate that plakoglobin may have a similar function to that of β-catenin within the Wnt signaling pathway. β-catenin is known to be an oncogene in many forms of human cancer, following acquisition of stabilizing mutations in amino terminal sequences. Kolligs and coworkers show, however, that unlike β-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 β-catenin in that it requires activation of the proto-oncogene c-myc. Surprisingly, c-myc is activated more efficiently by plakoglobin than β-catenin, despite its previous identification as a target of Tcf/β-catenin. In contrast, a synthetic Tcf reporter gene is activated to a much greater extent by β-catenin than plakoglobin. Plakoglobin and β-catenin may therefore have different roles in Wnt signaling and cancer, which reflect their differential effects on target gene activity. (C) 2000 John Wiley and Sons, Inc.