IGFBP2 plays an important role in heat shock protein 27-mediated cancer progression and metastasis

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.

Quantitative proteomic analysis of the association between decreasing O‑GlcNAcylation and metastasis in MCF‑7 breast cancer cells

“…Moreover, the present study supports the results of previous studies which have demonstrated that O-GlcNAc regulates the cellular stress responses via the expression of numerous HSPs, including HSP27 (14,33). HSP27 expression levels affect cell proliferation, migration and invasion abilities in several types of cancer, such as liver, prostate and breast cancer (34)(35)(36).…”

The clinicopathological and prognostic value of HSP27 in hepatocellular carcinoma: a systematic review and meta-analysis

“…Ultimately, 11 eligible articles were included in this meta-analysis. 15 – 25 As shown in Table 1 , these studies were published from 2000 to 2017, and included a total of 876 HCC patients. The sample size ranged from 34 to 194 patients, with 6 of studies including >60 patients and 5 including ≤60 patients.…”

Decreasing O-GlcNAcylation affects the malignant transformation of MCF-7 cells via Hsp27 expression and its O-GlcNAc modification

“…Hsp27 was reported to be implicated in various cellular processes or even under pathologic disease conditions including cancer (28). Its expression level affects cell proliferation, migration and invasion in many types of cancer i.e., liver, prostate and breast cancer (29)(30)(31). Generally, Hsp27 is involved in the stress response mechanism which restores protein homeostasis (adaptive mechanism) in cancer cells.…”