英團(tuán)隊(duì)發(fā)現(xiàn)TIGAR介導(dǎo)的動(dòng)態(tài)ROS調(diào)控胰腺癌的發(fā)生和發(fā)展
2020-02-06
來(lái)源：小柯機(jī)器人
英國(guó)弗朗西斯·克里克研究所Karen H. Vousden團(tuán)隊(duì)取得一項(xiàng)新進(jìn)展，他們發(fā)現(xiàn)TIGAR介導(dǎo)的動(dòng)態(tài)ROS調(diào)控胰腺癌的發(fā)生和發(fā)展。相關(guān)論文于2020年1月23日在線發(fā)表于國(guó)際學(xué)術(shù)期刊《癌細(xì)胞》上。
使用胰腺導(dǎo)管腺癌（PDAC）模型，研究人員發(fā)現(xiàn)TIGAR對(duì)活性氧（ROS）的調(diào)節(jié)促進(jìn)了惡性腫瘤的起始，同時(shí)限制了轉(zhuǎn)移。PDAC細(xì)胞中ROS的增加會(huì)引起表型轉(zhuǎn)換，從而增加遷移、侵襲和轉(zhuǎn)移能力。此以轉(zhuǎn)換取決于MAPK信號(hào)的增加，可通過(guò)抗氧化劑治療來(lái)恢復(fù)。在小鼠和人類(lèi)中，TIGAR的表達(dá)在PDAC發(fā)育過(guò)程中受到調(diào)節(jié)，癌前病變中的TIGAR水平較高，而轉(zhuǎn)移性腫瘤中的TIGAR水平較低。這些研究表明，ROS的短暫、動(dòng)態(tài)調(diào)控促進(jìn)整個(gè)惡性進(jìn)展，并解釋了以往報(bào)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(jìn)腸道組織修復(fù)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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