The role of HSP90 molecular chaperones in hepatocellular carcinoma

Abstract

Misfolded proteins have enhanced formation of toxic oligomers and nonfunctional protein copies lead to recruiting wild‐type protein types. Heat shock protein 90 (HSP90) is a molecular chaperone generated by cells that are involved in many cellular functions through regulation of folding and/or localization of large multi‐protein complexes as well as client proteins. HSP90 can regulate a number of different cellular processes including cell proliferation, motility, angiogenesis, signal transduction, and adaptation to stress. HSP90 makes the mutated oncoproteins able to avoid misfolding and degradation and permits the malignant transformation. As a result, HSP90 is an important factor in several signaling pathways associated with tumorigenicity, therapy resistance, and inhibiting apoptosis. Clinically, the upregulation of HSP90 expression in hepatocellular carcinoma (HCC) is linked with advanced stages and inappropriate survival in cases suffering from this kind of cancer. The present review comprehensively assesses HSP90 functions and its possible usefulness as a potential diagnostic biomarker and therapeutic option for HCC.

The Disassociation of the A20/HSP90 Complex via Downregulation of HSP90 Restores the Effect of A20 Enhancing the Sensitivity of Hepatocellular Carcinoma Cells to Molecular Targeted Agents

“…Previously, HSP90 was considered an essential molecular chaperone that participates in physical processes, including protein homeostasis, cellular apoptosis, migration/invasion, and cellular signaling transduction ( 53 ). Studies have provided clues that HSPs functions as an essential regulator of HCC and overexpression of HSP90 ( 54 ). HSP90 is often associated with poor outcome and antitumor treatment resistance ( 55 ).…”

A Review of Progress in Histone Deacetylase 6 Inhibitors Research: Structural Specificity and Functional Diversity

“…Moreover, HSP90 enables mutant oncoproteins to avoid misfolding and degradation and allows malignant transformation, which plays an important role in tumorigenesis. 95,96 On the other hand, HDAC6 is able to regulate the degradation of misfolded proteins by targeting HSP90 (a famous substrate of HDAC6), which process is essential for efficient oncogenic cell transformation. 26 HSP90 inhibitors have been identified as potential cancer therapeutics.…”

“…HSP90 is a cell-generated molecular chaperone involved in a variety of cellular functions by regulating the folding and/or localization of large multiprotein complexes and client proteins. Moreover, HSP90 enables mutant oncoproteins to avoid misfolding and degradation and allows malignant transformation, which plays an important role in tumorigenesis. , On the other hand, HDAC6 is able to regulate the degradation of misfolded proteins by targeting HSP90 (a famous substrate of HDAC6), which process is essential for efficient oncogenic cell transformation …”

MCT4 Promotes Hepatocellular Carcinoma Progression by Upregulating TRAPPC5 Gene

“…Although there have been significant advances in targeted drugs (antiangiogenic tyrosine kinase inhibitors) and immunotherapy (anti-PD1 agents) in recent years, the 5-year average survival rate of HCC patients is still less than 20%. 3 , 4 In addition to conventional clinicopathological factors such as lymph node metastasis, PNI, pathological grade, and staging, many molecules such as AFP, HSP90 and GPC-3 have been widely studied and applied as prognostic biomarkers involved in tumorigenesis and development, 5 , 6 more studies is needed to help providing effective treatment targets and prognostic markers.…”