TNFSF12A (Tumor Necrosis Factor Receptor Superfamily Member 12A), alias Fn14, is a protein implicated in the positive modulation of the extrinsic apoptotic signaling pathway and the regulation of wound healing processes. Positioned on the cellular surface and ruffles, TNFSF12A is anticipated to be functionally active within the plasma membrane. Conditions linked with TNFSF12A encompass glioblastoma and multiple sclerosis. Biological pathways linked to it encompass Akt signaling and interactions within the TNF superfamily - human ligand-receptor interactions and their associated functionalities.
Its Gene ID: 51330, UniProtKB ID: Q9NP84, and OMIM ID: 605914.
The cytokine TWEAK (tumor necrosis factor-like weak inducer of apoptosis) and its functional receptor, Fn14 (fibroblast growth factor-inducible 14, also known as TNFSF12A), exhibit abundant expression during pathological cardiovascular remodeling. Upon binding of soluble TWEAK to the extracellular domain of the Fn14 receptor, trimerization occurs, initiating a structural alteration in the receptor. This conformational change prompts the recruitment of TRAF proteins to the receptor's cytoplasmic tail, leading to activation of various signaling pathways including NF-κB, ERK/JNK/p38, AP-1, JAK/STAT, and PI3K/AKT. Enhanced activation of these pathways modulates specific target genes, thereby exerting biological effects such as proliferation, differentiation, and apoptosis regulation. The TWEAK/Fn14 axis governs diverse cellular functions implicated in inflammation and fibrosis, which are intricately associated with cardiovascular diseases.
Fig.1 Signaling pathway of TWEAK and Fn14.1, 3
Previous investigations into gene expression profiles among cancer patients have revealed mRNA overexpression of genes encoding TNFSF12A proteins in colorectal cancer patients. However, limited information exists regarding the protein-level expression of these genes. Currently, there is a lack of serum-based tests with adequate sensitivity and specificity for widespread application in identifying these cancer markers. To address this gap, we generated specific monoclonal antibodies targeting TNFSF12A and developed detection assays. Analysis of serum samples from colorectal cancer patients using ELISA DAS or multiplex ELISA assays revealed sensitivity levels at the pg marker per ml sample range. These findings suggest that TNFSF12A proteins are indeed expressed at the protein level in colorectal cancer patients, as detected in their serum. The antibodies produced against these cancer markers hold potential for facilitating early detection, thereby improving the diagnosis and prognosis of colorectal cancer.
TWEAK and its corresponding receptor TNFSF12A (TWEAKR) belong to the TNF and TNFR superfamilies, respectively, implicated in various critical biological processes such as development, hematopoiesis, inflammation, immune response, and tissue repair. These receptor-ligand pairs serve as promising targets for therapeutic interventions, with many compounds specifically designed against them either approved or in developmental stages for treating cancers or autoimmune disorders. To assess TNFSF12A expression in human breast cancers (BC), anti-TNFSF12A antibodies were utilized to evaluate their antitumor effects, either alone or following chemotherapy-induced complete remission. TNFSF12A protein expression was observed in most human BC samples, and the anti-TNFSF12A antibody demonstrated high efficacy in certain BC patient-derived xenograft models (PDXs). These findings underscore the therapeutic promise of targeting TNFSF12A in BC and suggest the potential for prospectively identifying patients who could benefit from such therapy. Combining a TNFSF12A-targeting agent with a treatment directed at epithelial-mesenchymal transition (EMT) induction may be of interest to promote mesenchymal-epithelial transition in tumor cells, thereby creating a more conducive environment for anti-TNFSF12A therapy.
Fig.2 Predictors of response to anti-TNFSF12A mAb.2, 3
Creative Biolabs provides high-quality anti-TNFSF12A antibody reagents designed for the exploration of cancer treatment strategies, particularly targeting colorectal cancer. Additionally, our esteemed customers can acquire personalized blocking antibody options centered around TNFSF12A.
Anti-TNFSF12A Neutralizing Antibody (V3S-1022-YC6032) (CAT#: V3S-1022-YC6032)
Target: TNFSF12A
Host Species: Human
Target Species: Human,
Application: ELISA,FC,IP,FuncS,IF,Neut,ICC,