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

Cheung, E. C., DeNicola, G. M., Nixon, C., Blyth, K., Labuschagne, C. F., Tuveson, D. A., Vousden, K. H. (January 2020) Dynamic ROS Control by TIGAR Regulates the Initiation and Progression of Pancreatic Cancer. Cancer Cell. ISSN 1535-6108

URL: https://www.ncbi.nlm.nih.gov/pubmed/31983610
DOI: 10.1016/j.ccell.2019.12.012


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.

Item Type: Paper
Subjects: diseases & disorders > cancer > metastasis
organism description > animal > mammal > rodent > mouse
diseases & disorders > cancer > cancer types > pancreatic cancer
CSHL Authors:
Communities: CSHL labs > Tuveson lab
CSHL Cancer Center Program > Cellular Communication in Cancer Program
Depositing User: Adrian Gomez
Date: 13 January 2020
Date Deposited: 31 Jan 2020 17:51
Last Modified: 29 Jun 2021 15:17
PMCID: PMC7008247
Related URLs:
URI: https://repository.cshl.edu/id/eprint/38948

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