Systems based instantiation of the core gene regulatory network underlying epithelial-to-mesenchymal transition: the liver cancer case

We extend a mathematical model that describe the core gene regulatory network that rules the epithelial-to-mesenchymal transition to instantiate the liver cancer case. Thus, we characterize the cell phenotypic transitions that shape the attractors landscape state trajectories that define the transition from a normal epithelial cell profile to a stem-like cell phenotype with a potentially tumorigenic behavior via an intermediary cell senescent state. Our goal is then to prepare the ground to address the systems based development of preventive therapeutic interventions based  on the application of formal state-based optimal control methodologies built around the redesign of the underlying stochastic epigenetic landscapes.  We are particularly interested in the design of control schemes based on the modulatory role that nutrition has on the inflammatory response. This because the rhythm of the epithelial-to-mesenchymal transition phenomena causally depends on the dynamical inflammatory response activated by exogenous disturbances.