Research Papers:
IGFBP2 plays an important role in heat shock protein 27-mediated cancer progression and metastasis
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Abstract
Chin-Sheng Hung1,2,3,*, Chien-Yu Huang2,4,*, Chia-Hwa Lee5, Wei-Yu Chen6,7, Ming-Te Huang2,4, Po-Li Wei2,3,8,9,10,11 and Yu-Jia Chang1,2,3,11
1Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC
2Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC
3Division of General Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei, Taiwan, ROC
4Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan, ROC
5School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan, ROC
6Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC
7Department of Pathology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan, ROC
8Division of Colorectal Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan, ROC
9Translational Laboratory, Department of Medical Research, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan, ROC
10Graduate Institute of Cancer Biology and Drug Discovery, Taipei Medical University, Taipei, Taiwan, ROC
11Cancer Research Center, Taipei Medical University Hospital, Taipei, Taiwan, ROC
*These authors contributed equally to this work
Correspondence to:
Po-Li Wei, email: [email protected]
Yu-Jia Chang, email: [email protected]
Keywords: HCC, Hsp27, IGFBP2
Received: February 08, 2017 Accepted: June 18, 2017 Published: July 05, 2017
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.
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