Systems-Level Properties of EGFR-RAS-ERK Signaling Amplify Local Signals to Generate Dynamic Gene Expression Heterogeneity

Alexander E. Davies, Michael Pargett, Stefan Siebert, Taryn E. Gillies, Yongin Choi, Savannah J. Tobin, Abhineet R. Ram, Vaibhav Murthy, Celina Juliano, Gerald Quon, Mina J. Bissell, John G. Albeck

Research output: Contribution to journalArticle

Abstract

This work establishes a fluorescent live-cell reporter system to monitor local communication between malignant and non-malignant breast cancer cells. This system reveals that the EGFR-RAS-ERK signaling network amplifies small ligand fluctuations to generate dynamically heterogeneous gene expression states, which may provide an adaptive advantage for tumor cells.

Original languageEnglish (US)
Pages (from-to)161-175.e5
JournalCell Systems
Volume11
Issue number2
DOIs
StatePublished - Aug 26 2020

Keywords

  • basal-like breast cancer
  • computational modeling
  • EGFR
  • ERK
  • MAPK
  • microenvironment
  • plasticity
  • RAS
  • scRNA-seq
  • systems biology

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology

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  • Cite this

    Davies, A. E., Pargett, M., Siebert, S., Gillies, T. E., Choi, Y., Tobin, S. J., Ram, A. R., Murthy, V., Juliano, C., Quon, G., Bissell, M. J., & Albeck, J. G. (2020). Systems-Level Properties of EGFR-RAS-ERK Signaling Amplify Local Signals to Generate Dynamic Gene Expression Heterogeneity. Cell Systems, 11(2), 161-175.e5. https://doi.org/10.1016/j.cels.2020.07.004