A plausible accelerating function of intermediate states in cancer metastasis

PLoS Comput Biol. 2020 Mar 10;16(3):e1007682. doi: 10.1371/journal.pcbi.1007682. eCollection 2020 Mar.

Abstract

Epithelial-to-mesenchymal transition (EMT) is a fundamental cellular process and plays an essential role in development, tissue regeneration, and cancer metastasis. Interestingly, EMT is not a binary process but instead proceeds with multiple partial intermediate states. However, the functions of these intermediate states are not fully understood. Here, we focus on a general question about how the number of partial EMT states affects cell transformation. First, by fitting a hidden Markov model of EMT with experimental data, we propose a statistical mechanism for EMT in which many unobservable microstates may exist within one of the observable macrostates. Furthermore, we find that increasing the number of intermediate states can accelerate the EMT process and that adding parallel paths or transition layers may accelerate the process even further. Last, a stabilized intermediate state traps cells in one partial EMT state. This work advances our understanding of the dynamics and functions of EMT plasticity during cancer metastasis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Computational Biology
  • Energy Metabolism
  • Epithelial-Mesenchymal Transition / physiology*
  • Humans
  • Markov Chains
  • Mice
  • Models, Biological*
  • Neoplasm Metastasis* / pathology
  • Neoplasm Metastasis* / physiopathology
  • Neoplasms / pathology
  • Neoplasms / physiopathology

Grants and funding

This project was supported by the ASU School of Biological and Health Systems Engineering and NSF grant (EF-1921412) (to X-JT) (https://www.nsf.gov/awardsearch/showAward?AWD_ID=1921412). HG and JRM-A were also supported by the Arizona State University Dean’s Fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.