Cellular Functions of Small Heat Shock Proteins (HSPB) in Hepatocellular Carcinoma

Abstract
Heat shock proteins (HSPs) play an essential role as molecular chaperones in proteostasis. Small HSPs are a group of low-molecular-weight HSPs in the range of 12-43 kDa and are classified as HSPB. Within the ten members of the family, HSPB1 (HSP27), HSPB5 (B-crystallin), HSPB6 (HSP20), and HSPB8 (HSP22) ubiquitously exist in various tissues, including liver tissue. These small HSPs undergo phosphorylation as a post-translational modification, and their functions are modulated. Hepatocellular carcinoma (HCC) is one of the most frequent cancers and the fourth leading cause of cancer-related death worldwide. HSPs play a cytoprotective role as molecular chaperones. Thus, HSPB has been generally considered to protect HCC cells and help the progression of HCC. On the other hand, recent studies from our laboratories have demonstrated suppressive roles of phospho-HSPB1, HSPB6, and HSPB8 in progression of HCC. These findings may provide a basis for a novel defense system by HSPB against HCC progression. This review focuses on the cellular functions of HSPB in HCC and summarizes the current research.