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An evolving model for Wnt/β-catenin signaling in melanoma.
This chart integrates results from existing transgenic mouse and human melanoma studies, as well as results from this study, into an evolving unified model that can be further tested for refinement. Dashed lines/arrows indicate that studies leading to this part of the model utilized overexpression of a mutant (non-degradable) β-catenin in transgenic mice, which may or may not be applicable in patient melanomas where these mutations are quite rare . This model accounts for the clinical observation in multiple studies of improved survival with elevated nuclear β-catenin in tumors from molecularly unselected melanoma patients. In melanocytes as well as nevi, high levels of nuclear β-catenin and Wnt signaling are observed, and the loss of nuclear β-catenin correlates with progression from benign melanocytic lesions to melanoma.