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 insulinlike 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.

Original languageEnglish
Pages (from-to)54978-54992
Number of pages15
JournalOncotarget
Volume8
Issue number33
DOIs
Publication statusPublished - 2017

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HSP27 Heat-Shock Proteins
Intercellular Signaling Peptides and Proteins
Carrier Proteins
Neoplasm Metastasis
Neoplasms
Hepatocellular Carcinoma
Snails
beta Catenin
Vimentin
Luciferases
Heterografts
Genetic Promoter Regions
Small Interfering RNA
Cell Movement

Keywords

  • HCC
  • Hsp27
  • IGFBP2

ASJC Scopus subject areas

  • Oncology

Cite this

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title = "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 insulinlike 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.",
keywords = "HCC, Hsp27, IGFBP2",
author = "Hung, {Chin Sheng} and Huang, {Chien Yu} and Lee, {Chia Hwa} and Chen, {Wei Yu} and Huang, {Ming Te} and Wei, {Po Li} and Chang, {Yu Jia}",
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T1 - IGFBP2 plays an important role in heat shock protein 27-mediated cancer progression and metastasis

AU - Hung, Chin Sheng

AU - Huang, Chien Yu

AU - Lee, Chia Hwa

AU - Chen, Wei Yu

AU - Huang, Ming Te

AU - Wei, Po Li

AU - Chang, Yu Jia

PY - 2017

Y1 - 2017

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