TABLE 1.
Highlights of the two contradicting studies concerning HSP60 roles in HCC.
| HSP60 main function | HSP60 functions as tumor suppressor of HCCa | HSP60 supports the development and progression of HCCb |
| HSP60 levels | Both mRNA and protein levels are reduced in tumor tissues of HCC patients compared with peritumor tissues | In liver tissues of HCC patients, high levels of HSP60 were found in 56.6% of specimens compared to 40.0% with reduced HSP60 levels |
| Clinical correlation | HSP60 expression ratio in cancerous and pericancerous tissues of HCC patients [expressed as cancer/pericancer (C/P) ratio] is associated with overall survival. Low ratio is linked to poor overall survival and vice versa | No significant correlation between the quantitative variations of HSP60 expressed as paired tumor/non-tumor ratio (T/N) ratio and the clinical outcomes Only elevated HSP60 expression levels in non-cancerous tissues were associated with shorter overall survival. Moreover, there exists a positive correlation between HSP60 expression in non- cancerous tissues and macrovascular invasion, high tumor grades, and large tumor size |
| In vivo findings | Ectopic expression of Hsp60 in the left hepatic lobes of nude mice stimulated the differentiation and suppressed both intrahepatic and lung metastasis | Targeting HSP60 in mice xenograft models by jetPEI/HSP60-shRNA revealed significant reduction in both tumor size and weight compared to the control group |
| Molecular roles of HSP60 in HCC cells | HSP60 induced differentiation | Its role in differentiation was not experimentally investigated |
| HSP60 inhibited invasion and metastasis | Its role in metastasis was not experimentally investigated | |
| HSP60 promotes mitochondrial biogenesis | No significant alterations in mitochondrial mass upon HSP60-silencing in HCC cells | |
| No effect on proliferation | HSP60 silencing resulted in marked suppression of cell growth and proliferation | |
| No effect on apoptosis | HSP60 silencing destabilized survivin and promoted cell death | |
| Conclusion | Hsp60 exerts a tumor suppressor function, and might be utilized as a potential therapeutic target in the treatment of HCC | HSP60 can serve as prognostic marker as well as a therapeutic target for HCC |
a,bStudies performed by Zhang et al. (2016) and Huang et al. (2018), respectively.