ER proteostasis addiction in cancer biology: Novel concepts

Estefanie Dufey; Hery Urra; Claudio Hetz

doi:10.1016/j.semcancer.2015.04.003

ER proteostasis addiction in cancer biology: Novel concepts

Semin Cancer Biol. 2015 Aug:33:40-7. doi: 10.1016/j.semcancer.2015.04.003. Epub 2015 Apr 27.

Authors

Estefanie Dufey¹, Hery Urra¹, Claudio Hetz²

Affiliations

¹ Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, Center for Molecular Studies of the Cell, Faculty of Medicine, University of Chile, Santiago, Chile.
² Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, Center for Molecular Studies of the Cell, Faculty of Medicine, University of Chile, Santiago, Chile; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA. Electronic address: chetz@hsph.harvard.edu.

PMID: 25931388
DOI: 10.1016/j.semcancer.2015.04.003

Abstract

Endoplasmic reticulum (ER) stress is generated by various physiological and pathological conditions that induce an accumulation of misfolded proteins in its lumen. ER stress activates the unfolded protein response (UPR), an adaptive reaction to cope with protein misfolding to and restore proteostasis. However, chronic ER stress results in apoptosis. In solid tumors, the UPR mediates adaptation to various environmental stressors, including hypoxia, low in pH and low nutrients availability, driving positive selection. Recent findings support the concept that UPR signaling also contributes to other relevant cancer-related event that may not be related to ER stress, including angiogenesis, genomic instability, metastasis and immunomodulation. In this article, we overview novel discoveries highlighting the impact of the UPR to different aspects of cancer biology beyond its known role as a survival factor to the hypoxic environment observed in solid tumors.

Keywords: Cancer; ER stress; Proteostasis; UPR.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Apoptosis / genetics
Endoplasmic Reticulum / metabolism*
Endoplasmic Reticulum Stress
Humans
Hydrogen-Ion Concentration
Hypoxia
Neoplasm Metastasis
Neoplasms / metabolism*
Neovascularization, Pathologic
Protein Denaturation
Protein Folding
Signal Transduction / genetics
Unfolded Protein Response*