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Review
. 2016 Nov;283(22):4047-4055.
doi: 10.1111/febs.13764. Epub 2016 Jun 10.

The stress response paradox: fighting degeneration at the cost of cancer

Sonja L B Arneaud  1 , Peter M Douglas  1   2
Affiliations
Review

The stress response paradox: fighting degeneration at the cost of cancer

Sonja L B Arneaud et al. FEBS J. 2016 Nov.

Abstract

In the modern research era, sequencing and high-throughput analysis have linked genetic factors with a multitude of disease states. Often times, the same cellular machinery is implicated in several different diseases and has made it challenging to drug a particular disease with minimal pleotropic consequences. It is intriguing to see how different fields of disease research can present such differing views when describing the same biological process, pathway, or molecule. As observations in one field converge with research in another, we gain a more complete picture of a biological system and can accurately assess the feasibility for translational science. As an example discussed here, modulating latent stress response pathways within the cell provides exciting therapeutic potential, however, opposing views have emerged in the fields of degenerative disease and cancer. This at first glance seems logical as suppression of degenerative disease entails maintaining cell viability, while cancer aims to enhance selective senescence and cell death. As both of these disciplines seek novel therapeutic interventions, we should not overlook how scientific biases involving one biological process may impact different disease paradigms.

Keywords: Caenorhabditis elegans; aging; cancer; degeneration; heat shock factor; heat shock response; neurodegeneration; proteotoxic stress; stress.

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Figures

Fig. 1
Fig. 1
Regulation of protein homeostasis by HSF1. The proteostasis model depicts the ‘life of protein’ and includes synthesis, folding, processing, degradation, and aggregation of an arbitrary protein. HSF1 intervention within the pathway is denoted with red asterisks (*).
Fig. 2
Fig. 2
Maintaining HSF1 expression levels to achieve healthy homeostasis. Aberrant regulation of HSF1 protein levels can disrupt the delicate homeostatic balance and initiate different disease states. Elevated expression of HSF1 drives oncogenic initiation and metastasis, while depletion of HSF1 makes tissues more susceptible to degeneration.
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