NF-κB as a Critical Link Between Inflammation and Cancer

Abstract

NF-κB transcription factors have been suspected to be involved in cancer development since their discovery because of their kinship with the v-Rel oncogene product. Subsequent work led to identification of oncogenic mutations that result in NF-κB activation in lymphoid malignancies, but most of these mutations affect upstream components of NF-κB signaling pathways, rather than NF-κB family members themselves. NF-κB activation has also been observed in many solid tumors, but so far no oncogenic mutations responsible for NF-κB activation in carcinomas have been identified. In such cancers, NF-κB activation is a result of underlying inflammation or the consequence of formation of an inflammatory microenvironment during malignant progression. Most importantly, through its ability to up-regulate the expression of tumor promoting cytokines, such as IL-6 or TNF-α, and survival genes, such as Bcl-X_L, NF-κB provides a critical link between inflammation and cancer.