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Open Access Highly Accessed Review

Unfolded protein response in cancer: the Physician's perspective

Xuemei Li1, Kezhong Zhang2 and Zihai Li3*

Author Affiliations

1 Lea's Foundation Center for Hematologic Disorders and Neag Comprehensive Cancer Center, University of Connecticut School of Medicine, Farmington, CT 06030-1601, USA

2 Center for Molecular Medicine and Genetics, Department of Microbiology and Immunology, Wayne State University, Detroit, MI 48201, USA

3 Department of Microbiology & Immunology; Medical University of South Carolina, Charleston, SC 29425, USA

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Journal of Hematology & Oncology 2011, 4:8  doi:10.1186/1756-8722-4-8

Published: 23 February 2011

Abstract

The unfolded protein response (UPR) is a cascade of intracellular stress signaling events in response to an accumulation of unfolded or misfolded proteins in the lumen of the endoplasmic reticulum (ER). Cancer cells are often exposed to hypoxia, nutrient starvation, oxidative stress and other metabolic dysregulation that cause ER stress and activation of the UPR. Depending on the duration and degree of ER stress, the UPR can provide either survival signals by activating adaptive and antiapoptotic pathways, or death signals by inducing cell death programs. Sustained induction or repression of UPR pharmacologically may thus have beneficial and therapeutic effects against cancer. In this review, we discuss the basic mechanisms of UPR and highlight the importance of UPR in cancer biology. We also update the UPR-targeted cancer therapeutics currently in clinical trials.