Dynamic ROS Control by TIGAR Regulates the Initiation and Progression of Pancreatic Cancer.,Cancer Cell

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Dynamic ROS Control by TIGAR Regulates the Initiation and Progression of Pancreatic Cancer.
Cancer Cell ( IF 48.8 ) Pub Date : 2020-01-13 , DOI: 10.1016/j.ccell.2019.12.012
Eric C Cheung ₁ , Gina M DeNicola ₂ , Colin Nixon ₃ , Karen Blyth ₄ , Christiaan F Labuschagne ₁ , David A Tuveson ₅ , Karen H Vousden ₁

Affiliation

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：

TIGAR 的动态 ROS 控制调节胰腺癌的发生和进展。

TIGAR 蛋白具有抗氧化活性，支持肠道组织修复和腺瘤发展。使用胰腺导管腺癌 (PDAC) 模型，我们表明 TIGAR 的活性氧 (ROS) 调节支持癌前肿瘤的发生，同时限制转移。 PDAC 细胞中 ROS 的增加会驱动表型转换，从而增加迁移、侵袭和转移能力。这种转换依赖于 MAPK 信号激活的增加，并且可以通过抗氧化治疗来恢复。在小鼠和人类中，TIGAR 表达在 PDAC 发育过程中受到调节，癌前病变中 TIGAR 水平较高，转移性肿瘤中 TIGAR 水平较低。我们的研究表明，活性氧的暂时、动态控制是全面恶性进展的基础，有助于合理化抗氧化治疗的促肿瘤作用和抗肿瘤作用的相互矛盾的报告。

更新日期：2020-01-23

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