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。
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.