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 (αB-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 the 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.