Figure 7. FASN-regulated phenotype of breast cancer tissues.

A Waddingtonian perspective. Schematic visualization of the principle that FASN-regulated network rewiring causes a distortion of the attractor landscape (i.e., tissue architecture) that results in shift of attractor boundaries and allows a non-genetic switching between discrete phenotypic states (i.e., N: Normal; M: Malignant). Top. Despite schematic reduction of dimensionality, the developmental trajectory on the Waddingtonian epigenetic surface is established by “tissue states”, which are defined not only by gene-gene network interactions at the cellular level but rather extends beyond to include changes in the cell-cell interaction network including neovascularization and alterations in ECM turnover and mechanics. The status of FASN activation (vertical arrows) causes a normal tissue to become proliferative and mesenchymal by placing the tissue state (black circle) within the metastatic basin of attraction (red, top panel). Upon FASN inhibition, the non-proliferative and epithelial attractor (blue, bottom panel) is enlarged at the cost of the metastatic attractor (red), which shrinks as a consequence of the suppression of FASN. Bottom. Suppression of FASN-driven endogenous lipogenesis is sufficient to toggle the metastatic phenotype back to the original state by acting as a controller of attractor switching between self-propelling and self-stabilizing tissue states irrespective of genetic alterations.