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Review
. 2020 Apr 15:7:60.
doi: 10.3389/fmolb.2020.00060. eCollection 2020.

Heat Shock Protein 60 in Hepatocellular Carcinoma: Insights and Perspectives

Abdullah Hoter  1   2 , Sandra Rizk  3 , Hassan Y Naim  1
Affiliations
Review

Heat Shock Protein 60 in Hepatocellular Carcinoma: Insights and Perspectives

Abdullah Hoter et al. Front Mol Biosci. .

Abstract

Heat shock protein 60 (HSP60) is a mitochondrial chaperone that is implicated in physiological and pathological processes. For instance, it contributes to protein folding and stability, translocation of mitochondrial proteins, and apoptosis. Variations in the expression levels of HSP60 have been correlated to various diseases and cancers, including hepatocellular carcinoma (HCC). Unlike other HSPs which clearly increase in some cancers, data about HSP60 levels in HCC are controversial and difficult to interpret. In the current review, we summarize and simplify the current knowledge about the role of HSP60 in HCC. In addition, we highlight the possibility of its targeting, using chemical compounds and/or genetic tools for treatment of HCC.

Keywords: cancer therapy; chaperones; chaperonin; heat shock proteins; hepatocellular carcinoma; therapeutic resistance.

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Figures

FIGURE 1
FIGURE 1
Key factors contributing to hepatocellular carcinoma (HCC). These include chronic infections with infections with hepatitis B (HBV) or hepatitis C (HCV) virus, alcohol abuse, consumption of aflatoxins and non-alcoholic steatohepatitis (NASH).
FIGURE 2
FIGURE 2
A schematic representation summarizing the roles of HSP60 in regulating tumor cell apoptosis. Suppression of apoptosis by HSP60 is associated with increased levels of anti-apoptotic proteins like Bcl-2, Bcl-xL, and survivin. These molecules counteract the release of cytochrome c from mitochondria. Selectively in tumor cells, HSP60 forms a multichaperone complex with Cyclophilin D (Cyp D) and other chaperones including HSP90 and tumor necrosis factor receptor-associated protein 1 (TNFRP1) to maintain the mitochondrial permeability transition. Oncogenic HSP60 interacts with p53 in tumor cells and suppresses its action. HSP60 also controls the progression of apoptosis via regulating the mitochondrial release of smac/diablo and controlling the function of inhibitor of apoptosis (IAP) family proteins that inhibit caspases.
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