EP300 and cancer: To explain these dichotomous activities of Wnt signaling, recent data indicate that β-catenin/CBP-driven transcription is critical for proliferation without differentiation (e.g., in both normal and cancer stem/progenitor cells); whereas a switch to β-catenin/p300-mediated gene expression is an essential first step in initiating normal cellular differentiation [15], [16], [22], [33].