Chaperonins in cancer: Expression, function, and migration in extracellular vesicles

The chaperonins CCT and Hsp60 are molecular chaperones, members of the chaperone system (CS). Chaperones are cytoprotective but if abnormal in quantity or quality they may cause diseases, the chaperonopathies. Here, recent advances in the understanding of CCT and Hsp60 in cancerology are briefly discussed, focusing on breast and brain cancers. CCT subunits, particularly CCT2, were increased in breast cancer cells and this correlated with tumor progression. Experimental induction of CCT2 increase was accompanied by an increase of CCT3, 4, and 5, providing another evidence for the interconnection between the members of the CS and the difficulties expected while manipulating one member with therapeutic purposes. Another in silico study demonstrated a direct cor-relation between the increase in the tumor tissue of the mRNA levels of all CCT subunits, except CCTB6, with bad prognosis. Studies with glioblastomas demonstrated an increase in the CCT subunits in the tumor tissue and in extracellular vesicles (EVs) derived from them. Expression levels of CCT1, 2, 6A, and 7 were the most increased and markers of bad prognosis, particularly CCT6A. A method for measuring Hsp60 and related miRNA in exo-somes from blood of patients with glioblastomas or other brain tumors was discussed, and the results indicate that the triad Hsp60-related miRNAs-exosomes has potential regarding diagnosis and patient monitoring. All these data provide a strong foundation for future studies on the role played by chaperonins in carcinogenesis and for fully developing their theranostics applications along with exosomes.

Automated summary

This article briefly discusses the roles of CCT and Hsp60 in breast and brain cancers. Increased levels of CCT2 were found in breast cancer cells and correlated with tumor progression. Experimental induction of CCT2 increase also resulted in an increase of CCT3, 4, and 5, indicating the interconnection between members of the chaperone system. Studies on glioblastomas showed increased levels of CCT subunits in tumor tissue and extracellular vesicles derived from them. Measurement of Hsp60 and related miRNA in exosomes from blood of brain tumor patients could potentially be used for diagnosis and patient monitoring.