A family of proteins, known as transcription factors, regulate the biological process of converting DNA into RNA. Transcription factors can speed up or slow down the rate of transcription, and they allow the expression of unique genes in different cell types.
Nuclear Factor-kappa B (NF-κB) is a well-studied transcription factor that is highly involved in regulating genes engaged in physiological processes related to inflammation and immunity. The complexity of NF-κB is evident through its diverse effects on the immune system, especially in the anti-tumor immune response.
NF-κB, under different conditions, can both promote cancer growth and act as a tumor suppressor. An entire field of cancer research focuses on deciphering the positive and negative impacts of NF-κB. Several pro- and anti-cancer effects are associated with NF-κB imploring the (seasonal) question: Is NF-κB a trick or a treat for cancer?
The “tricks”: NF-κB as a tumor promotor
Activation of NF-κB promotes cancer cell survival by inducing the expression of genes that prevent apoptosis, the programmed death of cancer cells. NF-κB can also help cancer cells live longer by inducing the production of an enzyme called telomerase which prolongs the life of a cell by preventing the shortening of DNA, which happens with age.
Proto-oncogenes, genes that cause healthy cells to become cancerous, are also amplified by NF-κB. When proto-oncogenes are activated, they promote the rapid proliferation of cancer cells and fast-growing tumors. NF-κB also drives the production of inflammatory cytokines, and these factors directly stimulate tumor growth.
NF-κB also helps cancer to spread to secondary organs, a process known as metastasis. Metastasis occurs when NF-κB regulates the expression of adhesion molecules, genes that allow cancer cells to migrate through the blood to distant sites throughout the body where secondary cancer begins to form. Further, cancer cells require nutrients to grow, and these factors reach the tumor via blood vessels. NF-κB regulates additional genes involved in angiogenesis, the biological process by which new blood vessels form.
The “treats”: NF-κB as a tumor suppressor
Under certain circumstances, NF-κB can induce genes that promote apoptosis in cancer cells. NF-κB, when complexed with another gene, RelA, can stimulate the expression of apoptosis-inducing genes, such as Fas and Fas-ligand.
NF-κB can downregulate molecules that promote cancer growth resulting in tumor suppression. There are reports of NF-κB recruiting another protein, p53, which inhibits tumor growth.
An underappreciated benefit of NF-κB could be its use as a potential therapeutic target in novel therapies for cancer and other diseases. As our understanding of the paradoxical roles of NF-κB and the anti-tumor immune response deepens, ongoing research supporting the prevention and treatment of cancer will benefit.
The true face of NF-κB is likely dependent on the types of immune cells present in the vicinity of the tumor. If many regulatory cells, like regulatory T cells (Tregs) and myeloid derived suppressor cells (MDSCs), the expression of NF-κB promotes pro-tumor mechanisms. In the presence of innate immune cells like Natural Killer (NK) cells and macrophages, NF-κB supports an anti-tumor setting.