Fig. 5
The autocrine miR-200/TGF-β loop can maintain the mesenchymal phenotype. (a) The framework of TCS model with the autocrine miR-200/TGF-β loop. (b) Phase diagram of the circuit shown in (a) in response to an activation signal on SNAIL (S A ) and the production rate of endogenous TGF-β (\( {g}_{m_{TGF-\beta }} \)). Two different values of \( {g}_{m_{TGF-\beta }} \) are highlighted, as they are the values used to calculate the bifurcation in (c) and (d). (c) Bifurcation of ZEB1 mRNA levels in response to S A when \( {g}_{m_{TGF-\beta }}=2 \) molecules/h. (d) Bifurcation of ZEB1 mRNA level in response to S A when \( {g}_{m_{TGF-\beta }}=10 \) molecules/h. The arrow in (d) highlights that the mesenchymal state can be maintained without EMT-inducing signal S A when the basal production rate of endogenous TGF-β is high. Different colors in (b-d) represent different combinations of possible stable states