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Tumor necrosis factor receptor superfamily member 12A (TNFRSFA), also known as receptor fibroblast growth factor inducible 14 (FN14) TNFRSF12A (also known as receptor fibroblast growth factor inducible 14, FN14, CD266, TWEAKR) is induced by a large variety of growth factors including Fibroblast Growth Factor 1 (FGF1), FGF2, Platelet-Derived Growth Factor (PDGF), Epidermal Growth Factor (EGF) and Vascular Endothelial Growth Factor (VEGF), as well as cytokines such as tumor necrosis factor alpha (TNFalpha), Interleukin-1beta (IL-1beta), Interferon gamma (IFNgamma), and transforming growth factor-beta (TGF-beta). FN14 is expressed on a wide variety of different cell types and binds the ligand TWEAK (tumor necrosis factor-like weak inducer of apoptosis) to activate several signaling cascades through activation of NF-kappaB signaling mediated by adaptor TRAF proteins. The FN14/TWEAK pathway controls a range of cellular activities such as proliferation, differentiation, and apoptosis, and has diverse biological functions in pathological mechanisms like inflammation and fibrosis that are associated with cardiovascular diseases (CVDs). The complex is a positive regulator of cardiac hypertrophy and it has been shown that deletion of FN14 receptor protects from right heart fibrosis and dysfunction; the TWEAK/Fn14 axis could be a potential new therapeutic target for achieving cardiac protection in patients with CVDs. FN14 expression is also stimulated under specific atrophic conditions, such as denervation, immobilization, and starvation, leading to activation of TWEAK/Fn14 signaling and eventually skeletal muscle atrophy. FN14 is also a factor that promotes prostate cancer bone metastasis. |
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