G Protein-Coupled Receptor Connectivity to NF-B in Inflammation and Cancer

Complex intracellular network interactions regulate gene expression and cellular behavior. Whether at the site of inflammation or within a tumor, individual cells are exposed to a plethora of signals. The transcription factor nuclear factor-kappaB (NF-êB)regulates genes that control key cellular activities involved in inflammatory diseases and cancer. NF-êB is regulated by several distinct signaling pathways that may be activated individually or simultaneously. Multiple ligands and heterologous cell-cell interactions have an impact on NF-êB activity. The G protein-coupled receptor (GPCR)superfamily makes up the largest class of transmembrane receptors in the human genome and has multiple molecularly distinct natural ligands. GPCRs regulate proliferation, differentiation, and chemotaxis and play a major role in inflammatory diseases and cancer. Both GPCRs and NF-êB have been, and continue to be, major targets for drug discovery. A clear understanding of network interactions between GPCR signaling pathways and those that control NF-kB may be valuable for the development of better drugs and drug combinations.