Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway and associated cytokines (NF-κB pathway)

The tumor microenvironment (TME) cytokines and NF-κB pathway components constitute a complex signaling axis that integrates external inflammatory stimuli with intracellular transcriptional responses. In the TME, cytokines such as Tumor Necrosis Factor-alpha (TNF-α), Interleukin-1 (IL-1), and Interleukin-6 (IL-6) are secreted by both tumor cells and associated immune cells like macrophages [1][2]. These ligands bind to their respective receptors, triggering a cascade that activates the IκB kinase (IKK) complex, which in turn phosphorylates IκB proteins, marking them for proteasomal degradation [3]. This release allows the Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) transcription factor to translocate into the nucleus and activate genes involved in cell proliferation, anti-apoptosis, and angiogenesis [4]. Dysregulation of this pathway is a common feature in many cancers, where it promotes tumor progression, epithelial-mesenchymal transition (EMT), and resistance to therapy [5]. Pharmacological intervention often targets specific nodes within this network, such as using proteasome inhibitors like bortezomib or cytokine-neutralizing antibodies like infliximab [6].

Other names

NF-kappaB signalingTumor microenvironment cytokinesPro-inflammatory cytokine signalingIKK/NF-κB axisTumor microenvironment cytokines and NF-κB pathway components

Inhibition of the proteasome to prevent IκB degradation, neutralization of pro-inflammatory cytokines (TNF-α, IL-1, IL-6), and inhibition of IκB kinase (IKK) activity.