休眠肿瘤细胞是肿瘤复发转移的重要原因。微环境压力可以诱导DNA损伤，使细胞进入周期阻滞；也可以激活休眠细胞，但机制未明。最新发现，胞浆DNA识别受体cGAS不但可以识别胞浆微核，启动免疫清除效应；还可以诱导慢性炎症，甚至入核阻断DNA修复，促进肿瘤细胞增殖。我们发现，舌鳞癌微环境慢性炎症与间质纤维化形成复合压力，共同促进舌鳞癌发展；舌鳞癌cGAS表达与整合素、细胞周期相关蛋白以及慢性炎症因子相关。据此率先提出：微环境复合压力通过cGAS微核识别系统调控舌鳞癌细胞休眠及激活。拟构建多细胞3D打印舌鳞癌微环境复合压力模型，阐明微环境通过DNA损伤及信号传递双重途径对cGAS的调控作用，并在亚细胞定位、DNA结合能力、信号通路、细胞周期等方面阐明cGAS系统对细胞休眠及激活的调控机制，进而在体内外水平调控cGAS，探讨激活休眠舌鳞癌细胞并进行识别杀伤的作用模式，为舌鳞癌治疗提供新的思路及靶点。

Dormant tumor cells and their reawaken is one of the most important reason of cancer recurrence and metastasis. Microenvironment pressure can cause DNA damage to induce cycle arrest of tumor cells, and can also awaken dormant tumor cells, but the mechanism is uncertain. Recently, it is reported that cyclic GAP-AMP synthase (cGAS), a sensor of double-stranded DNA, not only can be activated by micronuclei in cytoplasm and cause innate immune response, but also can induce chronic inflammation, and even translocate into nuclear to suppress DNA repair and promote tumorigenesis. Our previous study showed that chronic inflammation and interstitial fibrosis contribute to each other and promote the development of tongue squamous cell carcinoma (TSCC); and the expression of cGAS in TSCC are associated with that of integrin family, cell cycle related proteins and chronic inflammation factors. Based on the studies above, we propose that composite pressure in tumor microenvironment can regulate dormancy and reawaken of TSCC cells though cGAS micronuclei sensor system. We will use 3D bio-printing to build dynamic model of TSCC microenvironment with composite pressure from tissue stiffness and chronic inflammation to illustrate the regulation of cGAS by tumor microenvironment, then to investigate the mechanism of regulating dormancy and reawaken of TSCC cell by cGAS system. At last we will regulate cGAS expression and function in vivo and in vitro to demonstrate the efficiency of “awaken dormant tumor cells to kill”policy, and to evaluate its significance in the treatment of TSCC.