Topological signatures in regulatory network enable phenotypic heterogeneity in small cell lung cancer.

ABSTRACT: Phenotypic (non-genetic) heterogeneity has significant implications for the development and evolution of organs, organisms, and populations. Recent observations in multiple cancers have unraveled the role of phenotypic heterogeneity in driving metastasis and therapy recalcitrance. However, the origins of such phenotypic heterogeneity are poorly understood in most cancers. Here, we investigate a regulatory network underlying phenotypic heterogeneity in small cell lung cancer, a devastating disease with no molecular targeted therapy. Discrete and continuous dynamical simulations of this network reveal its multistable behavior that can explain co-existence of four experimentally observed phenotypes. Analysis of the network topology uncovers that multistability emerges from two teams of player

SUBMITTER: Chauhan L 

PROVIDER: S-EPMC8012062 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature