The TIGAR protein has antioxidant activity that supports intestinal tissue repair and adenoma development. Using a pancreatic ductal adenocarcinoma (PDAC) model, we show that reactive oxygen species (ROS) regulation by TIGAR supports premalignant tumor initiation while restricting metastasis. Increased ROS in PDAC cells drives a phenotypic switch that increases migration, invasion, and metastatic capacity. This switch is dependent on increased activation of MAPK signaling and can be reverted by antioxidant treatment. In mouse and human, TIGAR expression is modulated during PDAC development, with higher TIGAR levels in premalignant lesions and lower TIGAR levels in metastasizing tumors. Our study indicates that temporal, dynamic control of ROS underpins full malignant progression and helps to rationalize conflicting reports of pro- and anti-tumor effects of antioxidant treatment.

中文翻译：

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TIGAR对ROS的动态控制可调节胰腺癌的发生和发展。

TIGAR蛋白具有抗氧化活性，可支持肠道组织修复和腺瘤发展。使用胰腺导管腺癌（PDAC）模型，我们显示TIGAR活性氧（ROS）调节支持恶性肿瘤的开始，同时限制转移。PDAC细胞中ROS的增加推动了表型转换，从而增加了迁移，侵袭和转移能力。此开关取决于MAPK信号转导的增加，可通过抗氧化剂治疗恢复。在小鼠和人类中，TIGAR表达在PDAC发育过程中受到调节，癌变前病变中TIGAR的水平较高，而转移性肿瘤中TIGAR的水平较低。我们的研究表明，时间，