Figure 4

Analysis of network motifs that arise after SMAD inhibition in the EMT network reveal an attractor landscape that is distinct from the unperturbed EMT network. The TGFβ-driven SMAD-perturbed EMT network (the EMT network with fixed TGFβ=ON and SMAD=OFF) has an almost identical mesenchymal state as the unperturbed network, as well as epithelial and mesenchymal states that are relatively different from the epithelial state of the unperturbed EMT model. We identify these relatively different states as hybrid epithelial-mesenchymal states. (a) The stable motifs associated with the hybrid epithelial–mesenchymal steady states and the sequence in which they stabilize after the TGFβ signal and SMAD suppression. The color of the node background indicates the node state; black corresponds to OFF and white corresponds to ON. The stable motif in the middle contains subsets of the stable motifs associated to the mesenchymal steady state (shown in b) but with the opposite states. These motifs are the Wnt/β-catenin stable motif (blue background), the AKT stable motif (red background), and the SHH stable motif (yellow background). (b) The stable motifs associated with the mesenchymal steady state in the TGFβ-driven SMAD-perturbed (TGFβ=ON; SMAD=OFF) EMT network and in the unperturbed EMT network. The color of the box that contains the stable motifs is the same as the background color used in a. EMT, Epithelial-to-mesenchymal transition, TGFβ, transforming growth factor beta.