Stem cells and TCF proteins: a role for beta-catenin--independent functions.

The Wnt signal transduction pathway has been shown to stimulate stem cell self renewal and has been shown to cause cancer in humans. One interesting aspect of Wnt signaling is that it utilizes downstream DNA-binding transcription factors, called Tcf proteins, which can activate transcription of target genes in the presence of a Wnt signal and repress the expression of target genes in the absence of a Wnt signal. Since Tcf proteins are present in Wnt-stimulated and unstimulated stem cells, understanding how Tcf proteins regulate target gene expression in each state offers the potential to understand how stem cells regulate their self-renewal, differentiation, and proliferation. In this article, we will review recent work elucidating the roles Tcf-protein interactions in the context of stem cells and cancer.