Ahn J, Konno H, Barber G N
Department of Cell Biology and Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, FL, USA.
Oncogene. 2015 Oct 8;34(41):5302-8. doi: 10.1038/onc.2014.457. Epub 2015 Feb 2.
Stimulator of interferon genes (STING) is a cellular sensor that controls cytosolic DNA-activated innate immune signaling. We have previously demonstrated that STING-deficient mice are resistant to carcinogen-induced skin cancer, similar to myeloid differentiation primary response gene 88 (MyD88) deficient mice, since the production of STING-dependent DNA-damage-induced proinflammatory cytokines, that likely require MyD88 signaling to exert their growth-promoting activity, are prevented. In contrast, MyD88-deficient mice are sensitive to colitis-associated cancer (CAC), since selected cytokines generated following DNA-damage also activate repair pathways, which can help prevent tumor development. Here, we demonstrate that STING signaling facilitates wound repair processes and that analogous to MyD88-deficient mice, STING-deficient mice (SKO) are prone to CAC induced by DNA-damaging agents. SKO mice harboring tumors exhibited low levels of tumor-suppressive interleukin-22 binding protein (IL-22BP) compared to normal mice, a cytokine considered critical for preventing colon-related cancer. Our data indicate that STING constitutes a critical component of the host early response to intestinal damage and is essential for invigorating tissue repair pathways that may help prevent tumorigenesis.
干扰素基因刺激因子（STING）是一种细胞传感器，可控制胞质DNA激活的先天性免疫信号传导。我们之前已经证明，STING缺陷小鼠对致癌物诱导的皮肤癌具有抗性，类似于髓样分化初级反应基因88（MyD88）缺陷小鼠，因为依赖STING的DNA损伤诱导的促炎细胞因子的产生被阻止，而这些细胞因子可能需要MyD88信号传导来发挥其促进生长的活性。相比之下，MyD88缺陷小鼠对结肠炎相关癌症（CAC）敏感，因为DNA损伤后产生的特定细胞因子也会激活修复途径，这有助于预防肿瘤发展。在这里，我们证明STING信号传导促进伤口修复过程，并且与MyD88缺陷小鼠类似，STING缺陷小鼠（SKO）容易受到DNA损伤剂诱导的CAC影响。与正常小鼠相比，患有肿瘤的SKO小鼠体内肿瘤抑制性白细胞介素-22结合蛋白（IL-22BP）水平较低，IL-22BP是一种被认为对预防结肠相关癌症至关重要的细胞因子。我们的数据表明，STING是宿主对肠道损伤早期反应的关键组成部分，对于激活可能有助于预防肿瘤发生的组织修复途径至关重要。
