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The unfolded protein response and cancer: a brighter future unfolding?

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Abstract

Mammalian cells are bathed in an interstitial fluid that has a tightly regulated composition in healthy states. Interstitial fluid provides cells with all the necessary metabolic substrates (oxygen, glucose, amino acids, etc.), and waste molecules are removed by diffusion gradients that are controlled by local vascular perfusion. The health and normal function of all cells within a body is dependent on the maintenance of this microenvironment. However, many disease states cause fluctuations in this, and in some instances, these might be of sufficient severity to stress and/or be toxic to the cell. Cells have developed a number of responses to enable their survival in a hostile environment. This article discusses one such pathway—the unfolded protein response and its relationship to cancer. The molecular signalling cascade, the mechanism of its activation in cancer and the consequences of its activation for a tumour are discussed, as are clinical studies and potential translational approaches for utilising this pathway for tumour targeting.

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Abbreviations

ER:

endoplasmic reticulum

Grp:

glucose-regulated protein

hsp:

heat shock protein

UPR:

unfolded protein response

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Authors and Affiliations

  1. Academic Unit of Surgical Oncology, University of Sheffield, K Floor, Royal Hallamshire Hospital, Glossop Road, Sheffield, S10 2JF, UK

    Peter Scriven, Nicola J. Brown & Lynda Wyld

  2. Immunobiology Research Unit, University of Sheffield, L Floor, Royal Hallamshire Hospital, Glossop Road, Sheffield, S10 2JF, UK

    A. Graham Pockley

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  1. Peter Scriven
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  2. Nicola J. Brown
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Correspondence to Peter Scriven.

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Scriven, P., Brown, N.J., Pockley, A.G. et al. The unfolded protein response and cancer: a brighter future unfolding?. J Mol Med 85, 331–341 (2007). https://doi.org/10.1007/s00109-006-0150-5

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  • DOI: https://doi.org/10.1007/s00109-006-0150-5

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