DcR3/TNFRSF6B Protein, Human (sf9, hFc)

Decoy Receptor 3 (DcR3), a secreted member of the Tumor Necrosis Factor (TNF) receptor superfamily, neutralizes three different TNF ligands/pro-apoptotic molecules: FasL, LIGHT, and TL1A. Each of these ligands engages unique signaling receptors which direct distinct and critical immune responses. Dcr3 has competitive binding with the functional receptors to the respective cytokines (Fas for FasL, DR3 for TL1A, and LTbR and herpesvirus entry mediator/HVEM for LIGHT), thus preventing downstream pro-apoptotic signaling. DcR3 is encoded by the Tnfrsf6b gene, which does not encode a cytoplasmic or transmembrane segment, resulting in an obligate secreted protein of 300 amino acids including the signal peptide. However, mouse and rat genomes lack a Tnfrsf6b gene^[1][2]. DcR3 is overexpressed in a wide variety of malignancies and is correlated with tumorigenesis and progression. Therefore, it has been considered a potential biomarker to predict cancer invasion and progression of inflammation. Specifically, DcR3 induces epithelial-mesenchymal transition through activation of the TGF-β3/SMAD signaling pathway in human colorectal cancer (CRC)^[3][4]. In addition, it increases the expression levels of several components of the PI3K/AKT/GSK-3β/β-catenin signaling pathway, such as p-AKT, GSK-3β, p-GSK-3β and β-catenin. Additionally, DcR3 also enhances the expression of N-cadherin and Vimentin and decreases the expression of E-cadherin^[3]. DcR3 also promotes proliferation and invasion of pancreatic cancer via a DcR3/STAT1/IRF1 feedback loop. It promotes the phosphorylation of signal transducers and activators of transcription 1 (STAT1), leading to a dramatic increase in interferon regulatory factor 1 (IRF1). IRF1 then increased the transcriptional activity of DcR3, forming a positive feedback loop to reinforce DcR3 expression^[5]. The homology of human DcR3 protein is low with that of other animals, and the sequence similarity with rats, mice and pigs is 20.49%, 20.82% and 20.00%, respectively.