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HSF1 and Molecular Chaperones in Biology and Cancer pp 113–131Cite as

The Impact of the ER Unfolded Protein Response on Cancer Initiation and Progression: Therapeutic Implications

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1243))

Abstract

Cellular stress induced by the accumulation of misfolded proteins in the endoplasmic reticulum (ER) activates an elaborate signalling network termed the unfolded protein response (UPR). This adaptive response is mediated by the transmembrane signal transducers IRE1, PERK, and ATF6 to decide cell fate of recovery or death. In malignant cells, UPR signalling may be required to maintain ER homeostasis and survival in the tumor microenvironment characterized by oxidative stress, hypoxia, lactic acidosis and compromised protein folding. Here we provide an overview of the ER response to cellular stress and how the sustained activation of this network enables malignant cells to develop tumorigenic, metastatic and drug-resistant capacities to thrive under adverse conditions. Understanding the complexity of ER stress responses and how to target the UPR in disease will have significant potential for novel future therapeutics.

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Acknowledgements

This work was supported by the NIH grants R01HL052173, R37DK042394, R24DK110973, R01DK103185, R01DK113171, R01AG062190 and R01CA198103 to R.J.K. and the NCI Cancer Center Support Grant P30 CA030199. R.J.K. is a member of the UCSD DRC (P30 DK063491) and Adjunct Professor in the Department of Pharmacology, UCSD. C.L. is a member of the UCSD DRC and is supported by the NIH grant T32DK007494.

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  1. Degenerative Diseases Program, SBP Medical Discovery Institute, La Jolla, CA, USA

    Cynthia Lebeaupin, Jing Yong & Randal J. Kaufman

  2. Department of Medicine, University of California San Diego, La Jolla, CA, USA

    Cynthia Lebeaupin

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  1. Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    Marc Laurence Mendillo

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  3. Weizmann Institute of Science, Rehovot, Israel

    Ruth Scherz-Shouval

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Lebeaupin, C., Yong, J., Kaufman, R.J. (2020). The Impact of the ER Unfolded Protein Response on Cancer Initiation and Progression: Therapeutic Implications. In: Mendillo, M.L., Pincus, D., Scherz-Shouval, R. (eds) HSF1 and Molecular Chaperones in Biology and Cancer. Advances in Experimental Medicine and Biology, vol 1243. Springer, Cham. https://doi.org/10.1007/978-3-030-40204-4_8

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