Hybrid E/M Phenotype(s) and Stemness: A Mechanistic Connection Embedded in Network Topology.

ABSTRACT: Metastasis remains an unsolved clinical challenge. Two crucial features of metastasizing cancer cells are (a) their ability to dynamically move along the epithelial-hybrid-mesenchymal spectrum and (b) their tumor initiation potential or stemness. With increasing functional characterization of hybrid epithelial/mesenchymal (E/M) phenotypes along the spectrum, recent in vitro and in vivo studies have suggested an increasing association of hybrid E/M phenotypes with stemness. However, the mechanistic underpinnings enabling this association remain unclear. Here, we develop a mechanism-based mathematical modeling framework that interrogates the emergent nonlinear dynamics of the coupled network modules regulating E/M plasticity (miR-200/ZEB) and stemness (LIN28/let-7). Simulating the dynamics o

SUBMITTER: Pasani S 

PROVIDER: S-EPMC7794989 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature