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Dynamic ROS Control by TIGAR Regulates the Initiation and Progression of Pancreatic Cancer.
Cheung, Eric C; DeNicola, Gina M; Nixon, Colin; Blyth, Karen; Labuschagne, Christiaan F; Tuveson, David A; Vousden, Karen H.
Afiliación
  • Cheung EC; The Francis Crick Institute, London NW1 1AT, UK.
  • DeNicola GM; Department of Cancer Physiology, Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
  • Nixon C; Cancer Research UK Beatson Institute, Glasgow G61 1BD, UK.
  • Blyth K; Cancer Research UK Beatson Institute, Glasgow G61 1BD, UK; Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1QH, UK.
  • Labuschagne CF; The Francis Crick Institute, London NW1 1AT, UK.
  • Tuveson DA; Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
  • Vousden KH; The Francis Crick Institute, London NW1 1AT, UK. Electronic address: karen.vousden@crick.ac.uk.
Cancer Cell ; 37(2): 168-182.e4, 2020 02 10.
Article en En | MEDLINE | ID: mdl-31983610
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Especies Reactivas de Oxígeno / Monoéster Fosfórico Hidrolasas / Péptidos y Proteínas de Señalización Intracelular / Proteínas Reguladoras de la Apoptosis Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Cancer Cell Asunto de la revista: NEOPLASIAS Año: 2020 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Especies Reactivas de Oxígeno / Monoéster Fosfórico Hidrolasas / Péptidos y Proteínas de Señalización Intracelular / Proteínas Reguladoras de la Apoptosis Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Cancer Cell Asunto de la revista: NEOPLASIAS Año: 2020 Tipo del documento: Article Pais de publicación: Estados Unidos