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The heat-shock, or HSF1-mediated proteotoxic stress, response in cancer: from proteomic stability to oncogenesis
The heat-shock, or HSF1-mediated proteotoxic stress, response in cancer: from proteomic stability to oncogenesis
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The heat-shock, or HSF1-mediated proteotoxic stress, response in cancer: from proteomic stability to oncogenesis
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The heat-shock, or HSF1-mediated proteotoxic stress, response in cancer: from proteomic stability to oncogenesis
The heat-shock, or HSF1-mediated proteotoxic stress, response in cancer: from proteomic stability to oncogenesis
Journal Article

The heat-shock, or HSF1-mediated proteotoxic stress, response in cancer: from proteomic stability to oncogenesis

2018
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Overview
The heat-shock, or HSF1-mediated proteotoxic stress, response (HSR/HPSR) is characterized by induction of heat-shock proteins (HSPs). As molecular chaperones, HSPs facilitate the folding, assembly, transportation and degradation of other proteins. In mammals, heat shock factor 1 (HSF1) is the master regulator of this ancient transcriptional programme. Upon proteotoxic insults, the HSR/HPSR is essential to proteome homeostasis, or proteostasis, thereby resisting stress and antagonizing protein misfolding diseases and ageing. Contrasting with these benefits, an unexpected pro-oncogenic role of the HSR/HPSR is unfolding. Whereas HSF1 remains latent in primary cells without stress, it becomes constitutively activated within malignant cells, rendering them addicted to HSF1 for their growth and survival. Highlighting the HSR/HPSR as an integral component of the oncogenic network, several key pathways governing HSF1 activation by environmental Stressors are causally implicated in malignancy. Importantly, HSF1 impacts the cancer proteome systemically. By suppressing tumour-suppressive amyloidogenesis, HSF1 preserves cancer proteostasis to support the malignant state, both providing insight into how HSF1 enables tumorigenesis and suggesting disruption of cancer proteostasis as a therapeutic strategy. This review provides an overview of the role of HSF1 in oncogenesis, mechanisms underlying its constitutive activation within cancer cells and its pro-oncogenic action, as well as potential HSFl-targeting strategies. This article is part of the theme issue 'Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective'.