Uncapping NF-κB activity in pancreatic cancer

Living cells must be capable of rapidly responding to intrinsic and environmental cues to ensure normal development and homeostasis. The NF-kappa B transcription factor mediates a series of such rapid-response programs, serving as a master regulator of gene transcription in cells subjected to inflammation, irradiation, or other stress states (Karin, 2009). While cells must be able to rapidly respond to NF-kappa B stimuli, it is similarly important to restrain sustained high NF-kappa B levels that can trigger chronic inflammation or cellular transformation. Results published by Lu et al (2011) in this issue of The EMBO Journal identify a novel mechanism that amplifies NF-kappa B activity; NF-kappa B upregulates mir301a, a microRNA (miRNA) that itself blocks the expression of an NF-kappa B inhibitor. The resulting positive feedback mechanism potentiates NF-kappa B target gene expression. While this pathway may be important for normal cellular stress responses, the authors show that its sustained induction in pancreatic cancer cells leads to constitutive NF-kappa B activity that drives tumour progression.