Cell shape and the microenvironment regulate nuclear translocation of NF-κB in breast epithelial and tumor cells.
Mol Syst Biol
; 11(3): 790, 2015 Mar.
Article
in En
| MEDLINE
| ID: mdl-26148352
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. Cellcell 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Breast
/
Cell Nucleus
/
NF-kappa B
Type of study:
Prognostic_studies
Limits:
Female
/
Humans
Language:
En
Journal:
Mol Syst Biol
Journal subject:
BIOLOGIA MOLECULAR
/
BIOTECNOLOGIA
Year:
2015
Type:
Article