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Measurements of Physiological Stress Responses in C. Elegans
Published on: May 21, 2020
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Stressing Out PanIN: NRF2 Pushes over the Edge
Laura Torrente1, Gina M DeNicola1
1Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
Cancer Cell
|December 13, 2017
Summary
Chronic stress promotes pancreatic cancer by impairing autophagy, a cellular process. This impairment activates NRF2 via p62, driving pancreatic ductal adenocarcinoma (PDAC) development.
Area of Science:
- Oncology
- Cellular Biology
- Stress Physiology
Background:
- Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy.
- The link between chronic stress and PDAC development is not well understood.
- Autophagy dysfunction is implicated in various cancers.
Purpose of the Study:
- To elucidate the mechanisms linking chronic stress to PDAC.
- To investigate the role of autophagy in stress-induced PDAC.
- To identify key molecular players in this process.
Main Methods:
- Utilized mouse models of PDAC.
- Assessed autophagy flux and p62 levels.
- Investigated NRF2 activation pathways.
Main Results:
- Chronic stress impairs autophagy in pancreatic cells.
- Impaired autophagy leads to p62 accumulation.
- p62 accumulation activates the NRF2 antioxidant pathway.
- NRF2 activation promotes PDAC development.
Conclusions:
- Impaired autophagy is a critical mechanism connecting chronic stress to PDAC.
- The p62-NRF2 axis is a key mediator of stress-induced PDAC.
- Targeting autophagy or NRF2 may offer therapeutic strategies for PDAC.
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