FKBP51 and the NF-κB regulatory pathway in cancer

Constitutive activation of NF-κB occurs in a significant percentage of human cancers. Genetic abnormalities of tumors often enhance normal NF-κB signaling. Chronic inflammation is also associated with constitutive NF-κB activation and increases the risk of cancer. Aberrant NF-κB activation favors cellular transformation, sustains cancer survival, and contributes to tumor invasion. Strategies to inhibit NF-κB represent a promising therapeutic option against cancer. In the last decade, several studies point to the large immunophilin FKBP51 as an important element for the control of NF-κB activation in human neoplasia. This article is an overview of the causes of aberrant NF-κB regulation in cancer and highlights recent papers that implicate FKBP51 in such deregulation.

► NF-κB is frequently deregulated in cancer.
► Constitutive activation of NF-κB sustains cancer survival, tumor invasion and therapy resistance.
► FKBP51 controls NF-κB activation in human neoplasia.
► FKBP51 is a potential target to overcome aberrant NF-κB.