NF-kB plays a role in our body’s immune responses to infection. When cells are invaded by viruses or bacteria or exposed to toxins or radiation, NF-kB becomes activated, which in turn regulates genes encoding cytokines, survival factors, cell cycle regulators, and adhesion molecules.
The concerted efforts lead to the activation and proliferation of immune cells, which ultimately kill or neutralize the pathogens.
In normal cells, NF-kB activation is tightly-regulated and transient. It returns to inactive status after infection or external stimulus is subsided.
However, there are pathogenic conditions that could lead to constitutive NF-kB activation. Hyper-activation of NF-kB could derive from gene mutations, prolonged exposure to carcinogens or factors in tumor micro-environment, or drug treatment.
Consequences of sustained NF-kB activation in cancers are tumor cell growth, drug resistance, and metastasis.
In Healthy Cells
Status: Inactivated by IkBs until receiving extracellular signaling
Role: Inflammation responses, Cell growth, Differentiation
In Cancer Cells
Status: Constitutively activated
Effect on tumor cells: Stimulate proliferation, Prevent apoptosis, Promote metastasis
Effect on tumor microenvironment: Promote MDSCs, Suppress CD8 T-cell activity on tumor
Effects on Cancer Initiating Cells: EMT