英團隊發(fā)現(xiàn)TIGAR介導的動態(tài)ROS調控胰腺癌的發(fā)生和發(fā)展
英國弗朗西斯·克里克研究所Karen H. Vousden團隊取得一項新進展，他們發(fā)現(xiàn)TIGAR介導的動態(tài)ROS調控胰腺癌的發(fā)生和發(fā)展。相關論文于2020年1月23日在線發(fā)表于國際學術期刊《癌細胞》上。
使用胰腺導管腺癌（PDAC）模型，研究人員發(fā)現(xiàn)TIGAR對活性氧（ROS）的調節(jié)促進了惡性腫瘤的起始，同時限制了轉移。PDAC細胞中ROS的增加會引起表型轉換，從而增加遷移、侵襲和轉移能力。此以轉換取決于MAPK信號的增加，可通過抗氧化劑治療來恢復。在小鼠和人類中，TIGAR的表達在PDAC發(fā)育過程中受到調節(jié)，癌前病變中的TIGAR水平較高，而轉移性腫瘤中的TIGAR水平較低。這些研究表明，ROS的短暫、動態(tài)調控促進整個惡性進展，并解釋了以往報道中抗氧化劑治療的促腫瘤和抗腫瘤作用的矛盾之處。
據(jù)介紹，TIGAR蛋白具有抗氧化活性，從而能夠促進腸道組織修復和腺瘤發(fā)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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