英团队发现TIGAR介导的动态ROS调控胰腺癌的发生和发展
英国弗朗西斯·克里克研究所Karen H. Vousden团队取得一项新进展，他们发现TIGAR介导的动态ROS调控胰腺癌的发生和发展。相关论文于2020年1月23日在线发表于国际学术期刊《癌细胞》上。
使用胰腺导管腺癌（PDAC）模型，研究人员发现TIGAR对活性氧（ROS）的调节促进了恶性肿瘤的起始，同时限制了转移。PDAC细胞中ROS的增加会引起表型转换，从而增加迁移、侵袭和转移能力。此以转换取决于MAPK信号的增加，可通过抗氧化剂治疗来恢复。在小鼠和人类中，TIGAR的表达在PDAC发育过程中受到调节，癌前病变中的TIGAR水平较高，而转移性肿瘤中的TIGAR水平较低。这些研究表明，ROS的短暂、动态调控促进整个恶性进展，并解释了以往报道中抗氧化剂治疗的促肿瘤和抗肿瘤作用的矛盾之处。
据介绍，TIGAR蛋白具有抗氧化活性，从而能够促进肠道组织修复和腺瘤发展。
附：英文原文
Title: Dynamic ROS Control by TIGAR Regulates the Initiation and Progression of Pancreatic Cancer
Author: Eric C. Cheung, Gina M. DeNicola, Colin Nixon, Karen Blyth, Christiaan F. Labuschagne, David A. Tuveson, Karen H. Vousden
Issue&Volume: January 23, 2020
Abstract: 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.
DOI: 10.1016/j.ccell.2019.12.012
Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(19)30582-3
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