Abstract
Heat shock protein 27 (Hsp27) is a key chaperone that interacts with over 200 client proteins. The expression of Hsp27 might be correlated with poor outcome in many types of cancer. Previous study indicated that Hsp27 might be an important biomarker in hepatocellular carcinoma (HCC). However, the detailed mechanism is less well understood. The shRNA-mediated silencing of Hsp27 decreased the proliferation, migration and invasion of HCC cells. In a xenograft model, the silencing of Hsp27 reduced tumor progression. We revealed that the silencing of Hsp27 led to a reduction in insulin-like growth factor binding protein 2 (IGFBP2), which might mediate proliferation and metastasis through vimentin, snail and beta-catenin. The overexpression of IGFBP2 reversed the reductions in cell growth, migration and invasion. The tissue array results showed that HCC patients with high Hsp27 expression exhibited poor prognosis and increased metastasis. The Hsp27 expression was highly correlated with IGFPB2 in CRC specimen. ChIP and luciferase assays showed that Hsp27 does not directly bind the IGFBP2 promoter region to regulate the transcription of IGFBP2. In conclusion, our study demonstrated that Hsp27 is a key mediator of HCC progression and metastasis and that Hsp27 might regulate proliferation and metastasis through IGFBP2. This pathway might provide a new direction for the development of a novel therapeutic strategy for HCC.
Highlights
Cancer is a major cause of morbidity and mortality worldwide, with 8.2 million cancer-related deaths in 2012
Heat shock protein 27 (Hsp27) is a major member of the heat shock protein family, and it was found to be correlated with cancer progression and poor prognosis
Our study demonstrates that insulinlike growth factor binding protein 2 (IGFBP2) is a novel downstream gene mediating the growth and invasiveness of hepatocellular carcinoma (HCC)
Summary
Cancer is a major cause of morbidity and mortality worldwide, with 8.2 million cancer-related deaths in 2012. Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death in the world, and approximately half of these deaths occur in China and Southeast Asia [1]. Despite progress in developing anti-cancer therapeutics, the outcome of HCC is still poor, and HCC usually causes death within 3 to 6 months in cases of unresectable disease [2, 3]. Early vaccination against hepatitis B virus can effectively prevent HCC [7,8,9], the inhibition of tumorigenesis after infection remains an important hurdle for the further control or prevention of HCC
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