Cell shape and the microenvironment regulate nuclear translocation of NF-κB in breast epithelial and tumor cells

Julia Sero, Heba Sailem, Rico Ardy, Hannah Almuttaqi, Zhang Tongli, Chris Bakal

Research output: Contribution to journalArticlepeer-review

76 Citations (Scopus)

Abstract

Although a great deal is known about the signaling events that promote nuclear translocation of NF-κB, how cellular biophysics and the microenvironment might regulate the dynamics of this pathway is poorly understood. In this study, we used high-content image analysis and Bayesian network modeling to ask whether cell shape and context features influence NF-κB activation using the inherent variability present in unperturbed populations of breast tumor and non-tumor cell lines. Cell–cell contact, cell and nuclear area, and protrusiveness all contributed to variability in NF-κB localization in the absence and presence of TNFα. Higher levels of nuclear NF-κB were associated with mesenchymal-like versus epithelial-like morphologies, and RhoA-ROCK-myosin II signaling was critical for mediating shape-based differences in NF-κB localization and oscillations. Thus, mechanical factors such as cell shape and the microenvironment can influence NF-κB signaling and may in part explain how different phenotypic outcomes can arise from the same chemical cues.
Original languageEnglish
Article number790
JournalMolecular Systems Biology
Volume11
Issue number3
DOIs
Publication statusPublished - 1 Mar 2015

Keywords

  • breast cancer
  • Cell Signalling
  • Mathematical modeling
  • NF-kappa B
  • GTPases
  • Cell shape
  • Cell adhesion
  • Single cell biology
  • High content imaging

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