Cell shape and the microenvironment regulate nuclear translocation of NF-κB in breast epithelial and tumor cells.
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Embargo End Date
ICR Authors
Authors
Sero, JE
Sailem, HZ
Ardy, RC
Almuttaqi, H
Zhang, T
Bakal, C
Sailem, HZ
Ardy, RC
Almuttaqi, H
Zhang, T
Bakal, C
Document Type
Journal Article
Date
2015-03-03
Date Accepted
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.
Citation
Molecular systems biology, 2015, 11 (3), pp. 790 - ?
Source Title
Publisher
WILEY
ISSN
1744-4292
eISSN
1744-4292
Collections
Research Team
Dynamical Cell Systems