Authors: Alexander Ring YongMi Kim Michael Kahn
Publish Date: 2014/05/14
Volume: 10, Issue: 4, Pages: 512-525
Abstract
Wnt signaling plays an important role in development and disease In this review we focus on the role of the canonical Wnt signaling pathway in somatic stem cell biology and its critical role in tissue homeostasis We present current knowledge how Wnt/βcatenin signaling affects tissue stem cell behavior in various organ systems including the gut mammary gland the hematopoietic and nervous system We discuss evidence that canonical Wnt signaling can both maintain potency and an undifferentiated state as well as cause differentiation in somatic stem cells depending on the cellular and environmental context Based on studies by our lab and others we will attempt to explain the dichotomous behavior of this signaling pathway in determining cell fate decisions and put special emphasis on the interaction of βcatenin with two highly homologous coactivator proteins CBP and p300 to shed light on the their differential role in the outcome of Wnt/βcatenin signaling Furthermore we review current knowledge regarding the aberrant regulation of Wnt/βcatenin signaling in cancer biology particularly its pivotal role in the context of cancer stem cells Finally we discuss data demonstrating that small molecule modulators of the βcatenin/coactivator interaction can be used to shift the balance between undifferentiated proliferation and differentiation which potentially presents a promising therapeutic approach to stem cell based disease mechanisms
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