Title:The Accomplices of NF-κB Lead to Radioresistance
Volume: 16
Issue: 4
Author(s): Miaomiao Bai, Xiaoxing Ma, Xiaolei Li, Xiaohui Wang, Qian Mei, Xiang Li, Zhiqiang Wu and Weidong Han
Affiliation:
Keywords:
Cancer, ionizing radiation, NF-κB, radioresistance, radiotherapy, signal transduction.
Abstract: Ionizing radiation (IR) plays an important role in the treatment of epithelial
tumors, such as lung and prostate cancer, by wounding and killing cancer cells. However,
IR also activates sophisticated anti-apoptotic transcriptional factors such that cancer
cells fail to repair DNA damage and obtain resistance to apoptosis under conditions
of radiotherapy. Among these transcription factors, the transcription factor nuclear
factor kappa B (NF-κB) is recognized as a key feature for protecting cells from apoptosis
in most cell types. Moreover, the induction of radioresistance is mediated by several genes that are regulated by NF-
κB. The primary purpose of this review is to introduce the studies of the signaling mechanisms of IR in NF-κB activation,
such as ROS/NF-κB, ATM or DNA-PK/MAPKK/ p90rsk, PI3K/AKT/IKK and k-ras/c-raf/ MEKK/ NF-κB pathways.
Moreover, we describe how the expression of the target genes (e.g., XIAP, A20, FLIP, Bcl-xL) are induced by NF-κB to
regulate the activation of survival signaling pathways and to inhibit apoptotic signaling pathways. In addition, IR activates
NF-κB to express cell cycle-specific genes, for example cyclin D1, which is associated with reinforcing radioresistance.
We exhibit the signaling pathways that are induced by IR stimulation of NF-κB and illustrate the molecular mechanisms
of radioresistance.
