Wnt Signaling in Stem Cells and Cancer Stem Cells: A Tale of Two Coactivators

Abstract Wnt signaling in stem cells plays critical roles in development, normal adult physiology, and disease. In this chapter, we focus on the role of the Wnt signaling pathway in somatic stem cell biology and its critical role in normal tissue homeostasis and cancer. Wnt signaling can both maintain potency and initiate differentiation in somatic stem cells, depending on the cellular and environmental context. Based principally on studies from our lab, we will explain the dichotomous behavior of this signaling pathway in determining stem cell fate decisions, placing special emphasis on the interaction of β-catenin with either of the two highly homologous Kat3 coactivator proteins, CBP and p300. We will also discuss our results, both preclinical and clinical, demonstrating that small molecule modulators of the β-catenin/Kat3 coactivator interaction can be safely utilized to shift the balance between maintenance of potency and initiation of differentiation.