Decoy Receptor 3  (诱骗受体 3)

诱饵受体 3 (DcR3) 是肿瘤坏死因子 (TNF) 受体超家族的一员，可中和三种不同的 TNF 配体/促凋亡分子：FasL，LIGHT 和 TL1A。这些配体中的每一种有独特的信号受体，而参与关键免疫反应。Dcr3 与各自细胞因子的功能受体竞争性结合 (Fas 用于 FasL，DR3 用于 TL1A，LTbR 和疱疹病毒进入介质/HVEM 用于LIGHT)，从而阻止下游促凋亡信号。DcR3 由 Tnfrsf6b 基因编码，该基因不编码细胞质或跨膜片段，从而产生包括信号肽在内的 300 个氨基酸的专性分泌蛋白。然而，小鼠和大鼠基因组缺乏 Tnfrsf6b 基因^[1][2]。DcR3 在多种恶性肿瘤中过表达，并与肿瘤发生和进展相关。因此，它被认为是预测癌症侵袭和炎症进展的潜在生物标志物。具体而言，DcR3 在人结直肠癌 (CRC) 中通过激活 TGF-β3/SMAD 信号通路诱导上皮-间质转化 (epithelial-mesenchymal transition, EMT)。此外，它还能提高 PI3K/AKT/GSK-3β/β-catenin 信号通路中多种成分的表达水平，如 p-AKT、GSK-3β、p-GSK-3β 和 β-catenin。此外，DcR3 还能增强 N-cadherin 和 Vimentin 的表达，降低 E-cadherin 的表达^[3][4]。
DcR3 还通过 DcR3/STAT1/IRF1 反馈环促进胰腺癌的增殖和侵袭。它促进信号转导器和转录激活因子 1 (STAT1) 的磷酸化，导致干扰素调节因子 1 (IRF1) 的显著增加。IRF1 反过来又增加了 DcR3 的转录活性，形成正反馈循环，强化 DcR3 表达^[5]。人的 DcR3 蛋白与其他动物的同源性低，与大鼠、小鼠、猪的序列相似度分别为 20.49%，20.82%，20.00%。

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.

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