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

ABSTRACT: Although a great deal is known about the signaling events that promote nuclear translocation of NF-?B, 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-?B 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-?B localization in the absence and presence of TNF?. Higher levels of nuclear NF-?B were associated with mesenchymal-like versus epithelial-like morphologies, and RhoA-ROCK-myosin II signaling was critical for mediating shape-based differences in NF-?B localization and oscillations. Thus, mechanical factors such as cell shape and the microenvironment can influence NF-?B signaling and may in part explain how different phenotypic outcomes can arise from the same chemical cues.

SUBMITTER: Sero JE 

PROVIDER: S-EPMC4380925 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature