NF-κB signaling and crosstalk during carcinogenesis

Abstract

Transcription factors (TFs) are proteins that control the transcription of genetic information from DNA to mRNA by binding to specific DNA sequences either on their own or with other proteins as a complex. TFs thus support or suppress the recruitment of the corresponding RNA polymerase. In general, TFs are classified by structure or function. The TF, Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), is expressed in all cell types and tissues. NF-κB signaling and crosstalk are involved in several steps of carcinogenesis including in sequences involving pathogenic stimulus, chronic inflammation, fibrosis, establishment of its remodeling to the precancerous niche (PCN) and transition of a normal cell to a cancer cell. Triggered by various inflammatory cytokines, NF-κB is activated along with other TFs with subsequent stimulation of cell proliferation and inhibition of apoptosis. The involvement of NF-κB in carcinogenesis provides an opportunity to develop anti-NF-κB therapies. The complexity of these interactions requires that we elucidate those aspects of NF-κB interactions that play a role in carcinogenesis, the sequence of events leading to cancer.

The NLRP3 Inflammasome as a Critical Actor in the Inflammaging Process

“…NF-κB facilitates cancer progression by promoting cell cycle advances through the expression of the cyclin genes (D1, D2, D3, and DE) and c-myc [ 141 , 142 , 143 , 144 , 145 ], which play active roles in cell cycle progression. Additionally, NF-κB promotes the expression of cell adhesion proteins, like CD54, metalloproteinases involved in tumor invasion, and angiogenic factors such as the vascular endothelial growth factor [ 146 ]. By its part, STAT3 is a transcription factor involved in the Janus kinase/signal transducer and activator of transcription (JAK–STAT) signaling pathway whose hyperactivation also leads to tumor progression.…”

Factors in Oncogenesis: Viral Infections in Ovarian Cancer

“…In cervical cancer, HPV DNA integration in the host genome, genomic rearrangement, involving structural changes at the HPV DNA integration site, and the activation of replication at viral integrated sequences contribute to oncogenesis [121][122][123]. Genetic alterations which foster carcinogenesis involve DNA methylation and nucleotide polymorphisms.…”

“…HPV infection also triggers inflammatory pathways, primarily targeting the central regulators of inflammation, the NF-κB, STAT3, and cyclooxygenase-prostaglandin (COX-PG) pathways. In oral cancer, HPV E6 activates the NF-κB pathway by interaction with p50, NF-kappa-B-inducing kinase (NIK), and TRAF-interacting protein; in parallel, E7 inhibits apoptosis by targeting TNF-α [123]. In cervical cancer, the HPV E6-mediated elevated activity of IL-17 and increased expression of IL-1β by HPV E7 activate NF-κB [124].…”

AMP‐activated protein kinase (AMPK) regulates autophagy, inflammation and immunity and contributes to osteoclast differentiation and functionabs

“…Recent studies have also shown indirect evidence that NF-κB regulates the differentiation and function of osteoclasts through activation of the B-cell receptor to promote Bruton's tyrosine kinase and the inhibitor of nuclear factor-κB kinase expression in lymphocytes. While the latter induced Toll-like receptor 7 and 8 (TLR7/8) following stimulation of TNF transcription, KS99, a small molecule inhibitor of tubulin polymerisation, was found to block osteoclast differentiation and function (Brücher et al, 2019). Thus, the immune effects of NF-κB signalling associated with the regulation of AMPK requires further investigation.…”