TNF

The TNF (tumour necrosis factor) and TNFR (TNF receptor) families play significant roles in cancer by regulating various processes involved in tumour development, progression, and immune responses. The TNF family consists of cytokines that include tumour necrosis factor-alpha (TNF-α), TNF-β, and several other members. TNF-α is a key cytokine with pleiotropic effects involved in inflammation, apoptosis, and immune regulation, whilst TNF-β (also known as lymphotoxin-alpha) shares structural and functional similarities with TNF-α. Other members of the TNF family, such as TRAIL (TNF-related apoptosis-inducing ligand), CD40L, and FasL, are also thought to play important roles in cancer. The TNFR family consists of cell surface receptors that bind to TNF family ligands. The family includes TNFR1 (p55), TNFR2 (p75), Fas (CD95), DR3 (Death receptor 3), DR4, DR5, and several others. TNFRs are expressed on various cell types, including cancer cells and immune cells. Upon ligand binding, TNFRs initiate intracellular signalling pathways that regulate cell survival, proliferation, apoptosis, and inflammation. TNFR1 activation leads to the assembly of a multiprotein signalling complex called the TNF receptor 1 signalling complex (TNF-RSC). The key components of this complex are TNFR1, the adaptor protein TNFR1-associated death domain (TRADD), receptor-interacting protein kinase 1 (RIPK1), and TNF receptor-associated factor 2 (TRAF2). Upon ligand binding, TNFR1 recruits TRADD, which then recruits TRAF2 and RIPK1. This complex can activate several downstream signalling pathways including: 1) NF-κB Pathway: TNFR1 signalling can activate the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. This leads to the translocation of NF-κB into the nucleus, where it regulates the expression of genes involved in inflammation, cell survival, and proliferation; 2) MAPK Pathway: TNFR1 signalling can activate mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAPK. Activation of these kinases can influence cell proliferation, survival, and apoptosis; 3) TNFR1 signalling can also trigger cell death pathways, such as apoptosis or necroptosis, depending on the cellular context. These pathways involve the activation of caspases or RIPK1-mediated signalling, respectively. Several pro- and anti-tumorigenic functions of TNF signalling have been identified and include: 1) Promoting inflammation. TNF-α and other TNF family members can promote inflammation, which contributes to tumour initiation and progression; 2) Immune regulation: TNF-α and other TNF family members can modulate immune responses, affecting the activation and function of immune cells, such as T cells, B cells, and natural killer cells, in the tumour microenvironment; 3) Cell survival and proliferation: TNFRs can activate pro-survival signalling pathways, promoting cell survival and proliferation in cancer cells. 4) Apoptosis induction: Some TNF family ligands, such as TRAIL, FasL, and TNF-α under certain conditions, can trigger apoptosis in cancer cells by binding to their respective receptors; 5) Sensitizing cancer cells to therapy. Activation of certain TNFRs, like DR4 and DR5, can sensitize cancer cells to apoptosis-inducing therapies, making them more susceptible to treatment. We provide a comprehensive product range of research reagents for investigating TNF, including TNF alpha antibodies, CD70 antibodies, DR5 antibodies, TNF alpha ELISA Kits, and TNF beta ELISA Kits. Explore our full TNF product range below and discover more, for less.