Department of Biotherapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
Int J Cancer. 2012 May 1;130(9):1971-80. doi: 10.1002/ijc.27318. Epub 2012 Jan 11.
SOCS1, a prototype molecule of the SOCS family, was initially defined as a suppressor of cytokine signaling. The molecular mechanisms of SOCS1-mediated functions have been subsequently identified by studies using gene knockout mice and gene silencing technology. As part of a negative feedback regulation, SOCS1 downregulates cytokine signaling through direct inhibition of the JAK tyrosine kinase and the signaling cascade of activated cytokine receptors, thereby attenuating cytokine-initiated signal transduction. Moreover, other studies have demonstrated that SOCS1 also downregulates TLR signaling through direct and indirect mechanisms. Both cytokine receptor and TLR signaling pathways mediate important functions in survival, maturation and differentiation of various types of cells and in the regulation of immune function. Abnormal expression of SOCS1 in tumor cells has been detected in various human cancers, where it is associated with dysregulation of cytokine receptor and TLR signaling to promote cell transformation. Recent studies on the function of SOCS1 in tumor cells have revealed its novel role in carcinogenesis. In this review, we will focus on the mechanism of action of SOCS1 in both tumor cells and antigen-presenting cells in the tumor microenvironment. The potential of using SOCS1 as a diagnostic marker and therapeutic target in tumor diagnosis, prognosis and treatment is discussed.
SOCS1 是 SOCS 家族的原型分子，最初被定义为细胞因子信号的抑制物。SOCS1 介导功能的分子机制随后通过使用基因敲除小鼠和基因沉默技术的研究得到了鉴定。作为负反馈调节的一部分，SOCS1 通过直接抑制 JAK 酪氨酸激酶和激活的细胞因子受体的信号级联反应，下调细胞因子信号，从而减弱细胞因子引发的信号转导。此外，其他研究表明 SOCS1 还通过直接和间接机制下调 TLR 信号。细胞因子受体和 TLR 信号通路在各种类型细胞的存活、成熟和分化以及免疫功能的调节中发挥重要作用。在各种人类癌症中都检测到肿瘤细胞中 SOCS1 的异常表达，其与细胞因子受体和 TLR 信号的失调有关，从而促进细胞转化。SOCS1 在肿瘤细胞中的功能的最近研究揭示了其在致癌作用中的新作用。在这篇综述中，我们将重点讨论 SOCS1 在肿瘤细胞和肿瘤微环境中的抗原呈递细胞中的作用机制。讨论了将 SOCS1 用作肿瘤诊断、预后和治疗中的诊断标记物和治疗靶标的潜力。
