Fig. 8

Plasticity of cancer stem-like cells between dormant and proliferative conditions in terms of c-Myc regulation by FBW7. CSCs exhibit the plasticity depending on the tumor microenvironment, which is why CSCs can efficiently escape from the attack of the anti-tumor combined modality therapy compared with non-CSCs. Given that c-Myc undergoes ubiquitin-proteasome-dependent degradation by FBW7, CSCs highly expressing CD44v and FBW7 and lowly expressing c-Myc tend to be quiescent (G₀/G₁ dormant phase). ROS-induced activation of canonical Wnt/β-catenin signal pathway is responsible for up-regulation of c-Myc at the invasive front enriched in CSCs [118,119,120]. Note that, even under the proliferative conditions, non-CSCs show the genetic and/or epigenetic heterogeneity