The NF-κB pathway. In unstimulated cells, the NF-κB subunits p65 and p50 are sequestered in the cytoplasm by IκB. Ligand binding to receptors (such as TNFα and TLR4) leads to the activation of the IKK complex, which then phosphorylates IκB. Phosphorylated IκB is then ubiquitinated and degraded by the proteasome system, leading to the release of p65 and p50. The heterodimer then translocates to the nucleus and initiates the expression of genes that regulate proliferation, cell death, invasion, migration and immune regulation. This is the canonical pathway; there is also a non-canonical pathway involving other NF-κB family members. Most of the studies on EOC have looked at the members of the canonical pathway.