Endoplasmic Reticulum Stress and the Hallmarks of Cancer
- Trends Cancer. 2016 May;2(5):252-262. doi: 10.1016/j.trecan.2016.03.007.
- 1. Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile; Center for Geroscience, Brain Health and Metabolism, Santiago, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile.
- 2. Institut National de la Santé et de la Recherche Médicale (INSERM) Equipe de Recherche Labellisée (ERL) 440-Oncogenesis, Stress, and Signaling, University of Rennes 1, 35000 Rennes, France; Centre de Lutte Contre le Cancer Eugène Marquis, Rennes, France.
- 3. Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile; Center for Geroscience, Brain Health and Metabolism, Santiago, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA; Buck Institute for Research on Aging, Novato, CA 94945, USA. Electronic address: [email protected].
Tumor cells are often exposed to intrinsic and external factors that alter protein homeostasis, thus producing endoplasmic reticulum (ER) stress. To cope with this, cells evoke an adaptive mechanism to restore ER proteostasis known as the unfolded protein response (UPR). The three main UPR signaling branches initiated by IRE1α, PERK, and ATF6 are crucial for tumor growth and aggressiveness as well as for microenvironment remodeling or resistance to treatment. We provide a comprehensive overview of the contribution of the UPR to Cancer biology and the acquisition of malignant characteristics, thus highlighting novel aspects including inflammation, invasion and metastasis, genome instability, resistance to chemo/radiotherapy, and angiogenesis. The therapeutic potential of targeting ER stress signaling in Cancer is also discussed.