One of the earliest genes identified with stem and early progenitor cells is the RNA-binding protein, Musashi1 (Msi1). Through gene profiling of mammary epithelial cells transduced with Msi1, a unique autocrine signaling pathway was identified that activates both the Wnt and Notch pathways. This process was associated with increased secretion of the growth factor, PLF1 and inhibition of the secreted Wnt pathway inhibitor, DKK3. Identification of PLF1 as an effector of these pathways in the absence of the DKK3 tumor suppressor provides a new avenue for investigating differences between normal and malignant tissues, and potentially targeting tumor stem cells.
