Epithelial plasticity and cancer stem cells: Major mechanisms of cancer pathogenesis and therapy resistance

Figure 3 Epithelial-mesenchymal transition regulatory network: Mutually exclusive inhibitory loops including miR-200family/Zeb; miR-34family/Snail; LIN28/let-7 bring about bistable switch between epithelial (E) and mesenchymal (M) phenotypes, control Epithelial-mesenchymal transition/mesenchymal-epithelial transition and stemness. Phenotypic stability factors like OVOL and GRHL2 couple to core-EMT decision making circuits and stabilize hybrid E/M phenotype. NF-κB controls LIN28/let-7 regulation and elevates the likelihood of hybrid E/M phenotype. Solid arrows represent the activation; solid lines represent the repression and circular loops represent the self-activation. Hybrid E/M: Hybrid epithelial/mesenchymal; NF-κB: Nuclear factor kappa B; miR: MicroRNA; EMT: Epithelial-mesenchymal transition.