HSP90: A Key Player in Metal-Induced Carcinogenesis?

  • P. L. Abreu
  • L. M. R. Ferreira
  • T. Cunha-Oliveira
  • M. C. Alpoim
  • A. M. UrbanoEmail author
Part of the Heat Shock Proteins book series (HESP, volume 19)


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.


Cadmium Carcinogenesis Hexavalent chromium HSP90 Nickel Stress response 



glucose regulated protein 94


hypoxia-inducible factor 1 alpha


heat shock elements


heat shock factor(s)


heat shock protein family


heat shock protein(s)


reactive oxygen species


tumor necrosis factor receptor-associated protein 1



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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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • P. L. Abreu
    • 1
  • L. M. R. Ferreira
    • 2
  • T. Cunha-Oliveira
    • 3
  • M. C. Alpoim
    • 3
    • 4
  • A. M. Urbano
    • 4
    • 5
    Email author
  1. 1.Instituto de Medicina Molecular João Lobo Antunes, Faculty of MedicineUniversity of LisbonLisbonPortugal
  2. 2.Department of Surgery and Diabetes CenterUniversity of California, San FranciscoSan FranciscoUSA
  3. 3.CNC – Center for Neuroscience and Cell BiologyUniversity of CoimbraCoimbra and CantanhedePortugal
  4. 4.Centro de Investigação em Meio Ambiente, Genética e Oncobiologia (CIMAGO) and Department of Life SciencesUniversity of CoimbraCoimbraPortugal
  5. 5.Molecular Physical Chemistry Research UnitUniversity of CoimbraCoimbraPortugal

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