Fig. 4
The inhibition of miR-34 by ZEB1 promotes the ‘irreversibility’ of complete EMT, as elucidated by the TCS model. (a) Bifurcation diagram of ZEB1 mRNA levels in response to the activation signal on SNAIL (S A ) when \( {\lambda}_{Z,{\mu}_{34}}=0,\kern0.5em 0.2,\kern0.5em 0.4,\kern0.5em 0.6,\kern0.5em 0.8,\kern0.5em 1 \). \( {\lambda}_{Z,{\mu}_{34}} \) is the fold-change parameter which represents the strength of ZEB1 inhibition on miR-34. \( {\lambda}_{Z,{\mu}_{34}}=1 \) represents that there is no inhibition from ZEB1 to miR-34. \( {\lambda}_{Z,{\mu}_{34}}=0 \) represents strong inhibition from ZEB1 to miR-34. The dotted line in the bifurcation highlights the value of activation signal S A  = 50∗103 molecules, which is used to calculate the effective landscape (− log(P))as shown in (b). (b) Effective landscape of EMT for \( {\lambda}_{Z,{\mu}_{34}}=1 \) (no feedback), \( {\lambda}_{Z,{\mu}_{34}}=0.6 \) (Intermediate feedback) and \( {\lambda}_{Z,{\mu}_{34}}=0 \) (strong feedback). The stable state corresponding to each basin is labeled. The larger the blue area surrounding a particular state is, the more frequently that stable state can be achieved