In this issue, a truly international collaboration among colleagues, Stuart Calderwood from the USA, Daniel Ciocca from Argentina, and Andre Arrigofrom France, has produced a comprehensive review on the relevance and mechanisms of action of the heat shock proteins—a group of proteins critical for the folding and unfolding of other proteins (Ciocca et al. 2012b). The discovery, dating back to 1962, was made after the curious observation that heat induced a specific pattern of “puffing” in Drosophila chromosomes (Ritossa 1962; Ritossa and O’Loughlin 1996; Schlesinger 1990). These “puffs” were the consequence of increased expression of heat shock proteins. Today, it is well known that different types of stress conditions, including inflammation, infection, hypoxia, starvation, and—particularly relevant for our community—exposure of chemicals can also increase the expression of these proteins (Choi et al. 2011; Chattopadhyay et al. 2011; Romero et al. 2010; Zainul, 2011; Stewart 2011).
Of particular emphasis in the review (Ciocca et al. 2012a, this issue) is the role of heat shock proteins in carcinogenesis and tumor development. When normal cells are transformed, they undergo several major changes, including altered metabolism (Stewart et al. 2012; Cadenas et al. 2012), redox status (Cadenas et al. 2010), cytoskeleton rearrangement (Martin et al. 2012), and reduced apoptosis susceptibility (Petry et al. 2010). However, an especially relevant step in cancer is the upregulation of heat shock proteins. In the review, the authors highlight mechanisms by which these heat shock proteins contribute to carcinogenesis, including:
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the stabilization of growth factor receptor, signaling proteins (e.g., Akt and PI3K) and oncogenes (Bcr/Abl, Raf-1 and mutated P53)
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anti-apoptotic activities (e.g., by inhibition of ASK1 or by stabilizing mitochondria
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the promotion of angiogenesis
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the potential activation of energy metabolism
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protein trafficking and DNA damage control
We highly recommend the contribution of Ciocca and colleagues to anyone with an interest in stress response and carcinogenesis.
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Cadenas, C., Marchan, R. & Bolt, H.M. Role of heat shock proteins in stress response and carcinogenesis. Arch Toxicol 87, 1–2 (2013). https://doi.org/10.1007/s00204-012-0985-1
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DOI: https://doi.org/10.1007/s00204-012-0985-1