DNA damage-induced nuclear factor-kappa B activation and its roles in cancer progression.

Abstract

DNA damage is a vital challenge to cell homeostasis. Cellular responses to DNA damage (DDR) play essential roles in maintaining genomic stability and survival, whose failure could lead to detrimental consequences such as cancer development and aging. Nuclear factor-kappa B (NF-κB) is a family of transcription factors that plays critical roles in cellular stress response. Along with p53, NF-κB modulates transactivation of a large number of genes which participate in various cellular processes involved in DDR. Here the authors summarize the recent progress in understanding DNA damage response and NF-κB signaling pathways. This study particularly focuses on DNA damage-induced NF-κB signaling cascade and its physiological and pathological significance in B cell development and cancer therapeutic resistance. The authors also discuss promising strategies for selectively targeting this genotoxic NF-κB signaling aiming to antagonize acquired resistance and resensitize refractory cancer cells to cytotoxic treatments.