Journal
INTERNATIONAL JOURNAL OF CANCER
Volume 138, Issue 8, Pages 1824-1834Publisher
WILEY
DOI: 10.1002/ijc.29723
Keywords
heat shock proteins; hepatocellular carcinoma; therapeutic resistance; metastasis
Categories
Funding
- National Key Sci-Tech Special Project of China [2012ZX10002011-004]
- National Natural Science Foundation of China [81301818, 81402278]
- Shanghai Jiao Tong University School of Medicine [YG2014MS44, BXJ201319]
- Renji Hospital [RJZZ12-008]
- State Key Laboratory of Oncogenes and Related Genes [SB14-03]
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Heat shock proteins (HSPs) are highly conserved proteins, which are expressed at low levels under normal conditions, but significantly induced in response to cellular stresses. As molecular chaperones, HSPs play crucial roles in protein homeostasis, apoptosis, invasion and cellular signaling transduction. The induction of HSPs is an important part of heat shock response, which could help cancer cells to adapt to stress conditions. Because of the constant stress condition in tumor microenvironment, HSPs overexpression is widely reported in many human cancers. In light of the significance of HSPs for cancer cells to survive and obtain invasive phenotype under stress condition, HSPs are often associated with poor prognosis and treatment resistance in many types of human cancers. It has been described that upregulation of HSPs may serve as diagnostic and prognostic markers in hepatocellular carcinoma (HCC). Targeting HSPs with specific inhibitor alone or in combination with chemotherapy regimens holds promise for the improvement of outcomes for HCC patients. In this review, we summarize the expression profiles, functions and molecular mechanisms of HSPs (HSP27, HSP70 and HSP90) as well as a HSP-like protein (clusterin) in HCC. In addition, we address progression and challenges in targeting these HSPs as novel therapeutic strategies in HCC.
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