The role of heat-shock proteins and chaperonins in the pathogenesis and progression of cancer

Abstract

The superfamily of molecular chaperones plays a cardinal role in the maintenance of protein stability and function through a complex system of cooperative mechanisms able to balance proteostasis at different levels, from the synthesis of peptides to their proper folding, oligomerization, subcellular localization, and biological depuration. While most chaperones are also heat-shock proteins and show the ability to bind and release client-proteins of different sizes in a dynamic equilibrium, there is a subset of molecular chaperones that show the property to seize single peptide chains rather than bulky molecules, such that the protein is sequestered within a molecular cage arrangement. These are the so called chaperonins. There is considerable evidence to relate both types of molecular chaperones in the development and/or progression of cancer. The expression of several molecular chaperones is induced in many types of tumor, to the point that they are currently considered novel prognostic biomarkers. These findings have led to the development of synthetic organic ligands with therapeutic purposes. Comparatively, the contribution of chaperonins to cancer has not received as much attention to date compared to conventional heat-shock proteins. In several pathologies, both types of molecular chaperones are induced and are released from the cell by a still poorly understood mechanism. Extracellular molecular chaperones stimulate anti-inflammatory responses, thereby inducing a negative feedback to control of inflammation, such that immunization with defined peptides of some chaperones prevents the development of certain diseases. In this chapter, it is summarized the state of the art for heat-shock proteins in tumor development and progression, and is analyzed the evidence for the emerging role of chaperonins complexes in oncology.