Dynamic ROS Control by TIGAR Regulates the Initiation and Progression of Pancreatic Cancer.

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 Cell

journal_title

Cancer cell

authors

Cheung EC,DeNicola GM,Nixon C,Blyth K,Labuschagne CF,Tuveson DA,Vousden KH

doi

10.1016/j.ccell.2019.12.012

subject

Has Abstract

pub_date

2020-02-10 00:00:00

pages

168-182.e4

issue

2

eissn

1535-6108

issn

1878-3686

pii

S1535-6108(19)30582-3

journal_volume

37

pub_type

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