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.
journal_name
Cancer Celljournal_title
Cancer cellauthors
Cheung EC,DeNicola GM,Nixon C,Blyth K,Labuschagne CF,Tuveson DA,Vousden KHdoi
10.1016/j.ccell.2019.12.012subject
Has Abstractpub_date
2020-02-10 00:00:00pages
168-182.e4issue
2eissn
1535-6108issn
1878-3686pii
S1535-6108(19)30582-3journal_volume
37pub_type
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