title: Cell shape and the microenvironment regulate   nuclear translocation of NF-κB in breast epithelial   and tumor cells.
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.
authors.forename: Julia E
authors.initials: JE
authors.lastname: Sero
authors.forename: Heba Zuhair
authors.initials: HZ
authors.lastname: Sailem
authors.forename: Rico Chandra
authors.initials: RC
authors.lastname: Ardy
authors.forename: Hannah
authors.initials: H
authors.lastname: Almuttaqi
authors.forename: Tongli
authors.initials: T
authors.lastname: Zhang
authors.forename: Chris
authors.initials: C
authors.lastname: Bakal
mesh_terms: D001499:Bayes Theorem; D001940:Breast / Q000166:cytology* / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D048430:Cell Shape; D060833:Cellular Microenvironment; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D016328:NF-kappa B / Q000378:metabolism*; D021381:Protein Transport; D015398:Signal Transduction
chemical_list: D016328:NF-kappa B