Figure 1

The association between the core regulatory circuits for EMT/MET and MAT/AMT.

(a) The core EMT/MET regulatory circuit consists of two coupled mutually inhibitory circuits (SNAIL/miR-34 and ZEB/miR-200). It can receive external EMT-inducing signals such as HGF and regulate the Rac1/RhoA circuit by inhibiting the translation of RhoA and Rac1 via miR-34 and miR-200. (b) The effective (reduced) circuit, where μ₁ represents the inhibition on RhoA by either miR-34 or miR-200 and μ₂ represents similar inhibition on Rac1. A solid arrow denotes activation and a solid bar denotes repression. A solid line represents transcriptional regulation, a dotted line represents indirect regulations on GTP loading or hydrolysis process via GEFs or GAPs and a dashed line represents translational inhibition by microRNAs (c) Dynamical system characteristics of the effective circuit. The plot shows the nullclines and possible steady states corresponding to equation (1). When μ₁ = μ₂ = 100 molecules, the circuit can be tri-stable (LH, LL, HL). Red nullcline is for and black nullcline is for . Green solid circles denote the stable steady states and green hollow circles denote the unstable steady states. Each stable state can be associated with a cell phenotype, as depicted by a cartoon beside them.