NF‐κB signaling in inflammation and cancer

Abstract

Since nuclear factor of κ‐light chain of enhancer‐activated B cells (NF‐κB) was discovered in 1986, extraordinary efforts have been made to understand the function and regulating mechanism of NF‐κB for 35 years, which lead to significant progress. Meanwhile, the molecular mechanisms regulating NF‐κB activation have also been illuminated, the cascades of signaling events leading to NF‐κB activity and key components of the NF‐κB pathway are also identified. It has been suggested NF‐κB plays an important role in human diseases, especially inflammation‐related diseases. These studies make the NF‐κB an attractive target for disease treatment. This review aims to summarize the knowledge of the family members of NF‐κB, as well as the basic mechanisms of NF‐κB signaling pathway activation. We will also review the effects of dysregulated NF‐κB on inflammation, tumorigenesis, and tumor microenvironment. The progression of the translational study and drug development targeting NF‐κB for inflammatory diseases and cancer treatment and the potential obstacles will be discussed. Further investigations on the precise functions of NF‐κB in the physiological and pathological settings and underlying mechanisms are in the urgent need to develop drugs targeting NF‐κB for inflammatory diseases and cancer treatment, with minimal side effects.

Tyrosine phosphatase SHP2 exacerbates psoriasis‐like skin inflammation in mice via ERK5‐dependent NETosis

“…Such positive regulation by SHP2, through dephosphorylation of TLR7 at Tyr1024, promotes the trafficking of TLR7 to the endosome and maintains excessive activation of TLR7/NF‐κB signaling, thus aggravating skin inflammation. 28 , 37 In addition, NETs’ formation is increased in both peripheral blood and lesion skin of psoriasis patients and correlates with disease severity. 38 However, whether there is a regulatory relationship between SHP2 and NETs in neutrophils and how SHP2 influences NETs to promote psoriasis remains unclear.…”

“…We revealed a novel regulation by SHP2 of TLR7‐mediated NF‐κB signaling activation in macrophages. Such positive regulation by SHP2, through dephosphorylation of TLR7 at Tyr1024, promotes the trafficking of TLR7 to the endosome and maintains excessive activation of TLR7/NF‐κB signaling, thus aggravating skin inflammation 28,37 . In addition, NETs’ formation is increased in both peripheral blood and lesion skin of psoriasis patients and correlates with disease severity 38 .…”

Thymoquinone Prevents Doxorubicin-induced Hepatic-injury by Mitigating the Impairment of Mitochondrial Respiration and Electron Transport

“…Natural extracts have been linked to therapeutic molecules that modulate oxidative stress-mediated toxicity, including acute liver failure [11]. Hepatic tissue MDA levels, SOD, and CAT activity were determined in hepatic cells to further investigate THY's protective effect.…”

“…Furthermore, excessive ROS production can cause inflammation by activating the transcription factor (NF-kB), resulting in the massive production of cell adhesion molecules, chemokines, and pro-inflammatory cytokines, thereby increasing DOX cytotoxicity. Research has found that the inflammation-related transcription factor NF-kB, as well as its interaction with apoptosis, can cause hepatic injury [10][11][12]. A variety of active herbal extracts or active components derived from herbal medicines have been shown in earlier studies to be highly effective at counteracting the adverse effects of DOX [13].…”

Dimethyl Fumarate Induces Apoptosis via Inhibition of NF-κB and Enhances the Effect of Paclitaxel and Adriamycin in Human TNBC Cells

“…Recently, NF-κB p65 (RELA) gene expression was reported to be increased in TNBC compared to that in other subtypes, deeply involved in TNBC stem cell survival, and activated during the recurrence of breast cancers, including TNBC [ 4 , 5 , 6 ]. NF-κB, a transcription factor that promotes cell proliferation, differentiation, and survival, is involved in tumorigenesis and cancer survival in various solid tumors, including pancreatic, lung, cervical, prostate, breast, and gastric cancers [ 7 ]. Therefore, NF-κB may be a new therapeutic target molecule for TNBC.…”