Uncovering the particularities of the dynamical interaction between cancer-related Epithelial-Mesenchymal Transition and the Mammalian Cell Cycle: a feedback-based Boolean networks interconnection approach

Abstract

Epithelial-to-Mesenchymal Transition (EMT) plays a key role in epithelial-cancer. The state trajectory of its underlying Gene Regulatory Network (GRN) includes three fixed-point attractors characterizing epithelial, senescent, and mesenchymal, cell phenotypes, which implies specific cell-to-cell and cell-to-tissue interactions. The interplay between the GRN driving EMT and the one regulating the Mammalian Cell Cycle (MCC) influences cancer- related cell growing and proliferation. We expose the characteristics of the network arising from the interconnection of the gene regulatory networks associated to EMT and MCC. Our purpose is twofold: first, to elucidate the dynamical properties of cancer-related gene regulatory networks. Subsequently, to propose a computational methodology to address the interconnection of networks related to cancer. Our approach is based on feedback-based interconnection of networks described in discrete Boolean terms.