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HSP90: A Key Player in Metal-Induced Carcinogenesis?

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Heat Shock Protein 90 in Human Diseases and Disorders

Part of the book series: Heat Shock Proteins ((HESP,volume 19))

Abstract

Three extensively used metals, cadmium, chromium and nickel, are established human carcinogens. The elucidation of the molecular and cellular mechanisms underlying the carcinogenicity of these metals has centered mostly on the signalling pathways that regulate cellular growth, differentiation and death. Unfortunately, our understanding of the involvement of these pathways in metal-induced carcinogenesis is still very incomplete. More recently, research has extended to include the impact of these metals on mechanisms not traditionally associated with cancer, but that are now increasingly viewed as playing a critical role in carcinogenesis. Among them is the stress response, a highly conserved mechanism employed by all cells for protection against protein damage. Indeed, all three metals induce proteotoxic stress, which warrants following this line of research. The present chapter will critically review published studies on the impact of carcinogenic metals on the expression of the heat shock protein 90 family (HSP90), one of the protein families that mediate the stress response. HSP90 has been consistently found to be overexpressed in many types of cancer and, significantly, HSP90 overexpression has been correlated with increased tumor growth, metastatic potential and resistance to chemotherapy.

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Abbreviations

Grp94:

glucose regulated protein 94

HIF-1α:

hypoxia-inducible factor 1 alpha

HSE:

heat shock elements

HSF:

heat shock factor(s)

HSP:

heat shock protein family

Hsp:

heat shock protein(s)

ROS:

reactive oxygen species

TRAP1:

tumor necrosis factor receptor-associated protein 1

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Acknowledgements

The authors apologize for any studies on the subject that were not mentioned in this review. The authors’ original work on the impact of hexavalent chromium on heat shock expression was funded by Centro de Investigação em Meio Ambiente, Genética e Oncobiologia (CIMAGO), Portugal (grant 16/12) and Fundação para a Ciência e a Tecnologia (FCT), Portugal (grants UID/Multi/00070/2019 and SFRH/BPD/101169/2014). The authors were also supported by the following FCT grants: PD/BD/128284/2017 (to PLA), SFRH/BD/91614/2012 (to LMRF), POCI-01-0145-FEDER-029297 (to TCO) and PTDC/MAR-BIO/6149/2014 (to MCA).

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Abreu, P.L., Ferreira, L.M.R., Cunha-Oliveira, T., Alpoim, M.C., Urbano, A.M. (2019). HSP90: A Key Player in Metal-Induced Carcinogenesis?. In: Asea, A., Kaur, P. (eds) Heat Shock Protein 90 in Human Diseases and Disorders. Heat Shock Proteins, vol 19. Springer, Cham. https://doi.org/10.1007/978-3-030-23158-3_11

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