NF-kappaB as a critical link between inflammation and cancer.

NF-kappaB 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-kappaB activation in lymphoid malignancies, but most of these mutations affect upstream components of NF-kappaB signaling pathways, rather than NF-kappaB family members themselves. NF-kappaB activation has also been observed in many solid tumors, but so far no oncogenic mutations responsible for NF-kappaB activation in carcinomas have been identified. In such cancers, NF-kappaB 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-alpha, and survival genes, such as Bcl-X(L), NF-kappaB provides a critical link between inflammation and cancer.