Nallar Shreeram C, Kalvakolanu Dhan V
Department of Microbiology and Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Department of Microbiology and Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Cytokine Growth Factor Rev. 2017 Feb;33:1-18. doi: 10.1016/j.cytogfr.2016.09.001. Epub 2016 Sep 15.
Cytokines induce cell proliferation or growth suppression depending on the context. It is increasingly becoming clear that success of standard radiotherapy and/or chemotherapeutics to eradicate solid tumors is dependent on IFN signaling. In this review we discuss the molecular mechanisms of tumor growth suppression by a gene product isolated in our laboratory using a genome-wide expression knock-down strategy. Gene associated with retinoid-IFN-induced mortality -19 (GRIM-19) functions as non-canonical tumor suppressor by antagonizing oncoproteins. As a component of mitochondrial respiratory chain, GRIM-19 influences the degree of "Warburg effect" in cancer cells as many advanced and/or aggressive tumors show severely down-regulated GRIM-19 levels. In addition, GRIM-19 appears to regulate innate and acquired immune responses in mouse models. Thus, GRIM-19 is positioned at nodes that favor cell protection and/or prevent aberrant cell growth.
细胞因子根据具体情况诱导细胞增殖或生长抑制。越来越清楚的是，标准放疗和/或化疗根除实体瘤的成功与否取决于干扰素信号传导。在这篇综述中，我们讨论了通过全基因组表达敲低策略在我们实验室分离出的一种基因产物抑制肿瘤生长的分子机制。视黄酸-干扰素诱导死亡率相关基因-19（GRIM-19）通过拮抗癌蛋白发挥非经典肿瘤抑制作用。作为线粒体呼吸链的一个组成部分，GRIM-19影响癌细胞中“瓦伯格效应”的程度，因为许多晚期和/或侵袭性肿瘤显示GRIM-19水平严重下调。此外，在小鼠模型中，GRIM-19似乎调节先天性和获得性免疫反应。因此，GRIM-19处于有利于细胞保护和/或防止异常细胞生长的节点上。
