It should be noted that specific properties of cancer stem cells are maintained not only by the endogenous signaling pathways (i.e. Notch, Shh, Wnt/β-catenin) and other complex biological processes (i.e. the EMT) but also by the external environment called the niche, while the lack of signals from the niche can lead to loss of self-renewal capacity [5–7]. The gene discussed is SHH; the disease is cancer.