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Theranostics 2016; 6(4):558-570. doi:10.7150/thno.14693 This issue Cite

Research Paper

A Targetable Molecular Chaperone Hsp27 Confers Aggressiveness in Hepatocellular Carcinoma

Yurong Zhang^1*, Xuemei Tao^1*, Guangzhi Jin^2*, Haojie Jin¹, Ning Wang¹, Fangyuan Hu¹, Qin Luo¹, Huiqun Shu¹, Fangyu Zhao¹, Ming Yao¹, Jingyuan Fang¹, Wenming Cong², Wenxin Qin^1✉, Cun Wang^1✉

1. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
2. Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University.
* These authors contribute equally to this work.

✉ Corresponding authors: Cun Wang; Mailing Address: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, No. 25/Ln 2200 Xie-Tu Road, Shanghai 200032, China; Tel: +86-21-64436572; Fax: +86-21-64432142; Email: cwangorg. Or Wenxin Qin; Mailing Address: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, No. 25/Ln 2200 Xie-Tu Road, Shanghai 200032, China; Tel: +86-21-64436581; Fax: +86-21-64432142; Email: wxqinedu.cn. More

Abstract

Heat shock protein 27 (Hsp27) is an ATP-independent molecular chaperone and confers survival advantages and resistance to cancer cells under stress conditions. The effects and molecular mechanisms of Hsp27 in HCC invasion and metastasis are still unclear. In this study, hepatocellular carcinoma (HCC) tissue array (n = 167) was used to investigate the expression and prognostic relevance of Hsp27 in HCC patients. HCC patients with high expression of Hsp27 exhibited poor prognosis. Overexpression of Hsp27 led to the forced invasion of HCC cells, whereas silencing Hsp27 attenuated invasion and metastasis of HCC cells in vitro and in vivo. We revealed that Hsp27 activated Akt signaling, which in turn promoted MMP2 and ITGA7 expression and HCC metastasis. We further observed that targeting Hsp27 using OGX-427 obviously suppressed HCC metastasis in two metastatic models. These findings indicate that Hsp27 is a useful predictive factor for prognosis of HCC and it facilitates HCC metastasis through Akt signaling. Targeting Hsp27 with OGX-427 may represent an attractive therapeutic option for suppressing HCC metastasis.

Keywords: Hsp27, hepatocellular carcinoma, metastasis, prognosis, OGX-427.

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