A systems biology approach to determine the equilibrium of the unfolded protein response
Rapid expansion of glioma cells coupled with inadequate vascularization increases levels of cellular stress and triggers the unfolded protein response (UPR), which is typical for many aggressive cancers. The UPR can be considered a survival response mechanism promoting an adaptation to a changing microenvironment. All three branches of the UPR can promote survival in response to stress, persisting or prolonged UPR however can result in apoptotic cell death.
The mechanisms that determine the cell fate decision during ER stress are not well understood but increasing evidence suggests that the multiple signals that determine specific outcomes are complex and highly integrated. Until now it is not clear at which point the decision of survival versus apoptosis is made. Quantitative measurements of the equilibrium of the three UPR pathways are not available yet, but it appears that the UPR in glioma, in dependency of its strength, has a strong impact on proliferation, invasion and apoptosis.
Keywords: Proteomics, Lipidomics, UPR