Cell shape and the microenvironment regulate nuclear translocation of NF-{kappa}B in breast epithelial and tumor cells

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 TNFα. 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.

Source: Molecular Systems Biology - March 3, 2015 Category: Molecular Biology Authors: Sero, J. E., Sailem, H. Z., Ardy, R. C., Almuttaqi, H., Zhang, T., Bakal, C. Tags: Quantitative Biology & Dynamical Systems, Signal Transduction Articles Source Type: research