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. 2018 Jul 6;9(52):29906–29920. doi: 10.18632/oncotarget.25692

Figure 2. Notch-induced EMT couples hybrid E/M, stem and sender/receiver (S/R) states.

Figure 2

(A) Bifurcation diagram of the cellular level of microRNA 200 (miR-200) as a function of external Notch ligands LEXT (Delta + Jagged). Continuous and dotted black lines denote stable and unstable solutions of the model respectively. The thick black horizontal arrow highlights the range of LEXT allowing a hybrid E/M state. Red dotted lines indicate the miR-200 range of epithelial, hybrid E/M and mesenchymal phenotypes. (B) Bifurcation diagram of the cellular levels of LIN-28 in response to LEXT. The cell falls into the stemness window at intermediate LIN-28 levels (violet-shaded horizontal region – see Methods for more details about defining the boundaries of stemness window). The yellow vertical region and black arrow highlight the range of LEXT levels enabling a stable hybrid E/M state. (C) Bifurcation diagram of NICD in response to LEXT. The hybrid E/M phenotype interval maps onto high levels of NICD corresponding to (high Notch, high Jagged) and therefore to a Sender/Receiver (S/R) phenotype (see Methods for more details about defining the boundaries of the Notch states). For this diagram, the coupling between EMT and STEM circuits is intermediate (λLIM-28 = λZEB = 0.5), external Notch receptor is NEXT = 104 molecules and NF–kB = 2.5 * 103 molecules.