title: A Targetable Molecular Chaperone Hsp27 Confers Aggressiveness in Hepatocellular Carcinoma.
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.
authors.affiliation: 1. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yurong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 1. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Tao
authors.affiliation: 2. Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University.
authors.forename: Guangzhi
authors.initials: G
authors.lastname: Jin
authors.affiliation: 1. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Haojie
authors.initials: H
authors.lastname: Jin
authors.affiliation: 1. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.affiliation: 1. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Fangyuan
authors.initials: F
authors.lastname: Hu
authors.affiliation: 1. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Luo
authors.affiliation: 1. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Huiqun
authors.initials: H
authors.lastname: Shu
authors.affiliation: 1. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Fangyu
authors.initials: F
authors.lastname: Zhao
authors.affiliation: 1. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yao
authors.affiliation: 1. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Fang
authors.affiliation: 2. Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University.
authors.forename: Wenming
authors.initials: W
authors.lastname: Cong
authors.affiliation: 1. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Wenxin
authors.initials: W
authors.lastname: Qin
authors.affiliation: 1. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Cun
authors.initials: C
authors.lastname: Wang
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000473:pathology* / Q000556:secondary; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D055551:HSP27 Heat-Shock Proteins / Q000032:analysis*; D006360:Heat-Shock Proteins; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008113:Liver Neoplasms / Q000473:pathology* / Q000556:secondary; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008819:Mice, Nude; D018832:Molecular Chaperones / Q000032:analysis*; D009361:Neoplasm Invasiveness; D051058:Oncogene Protein v-akt / Q000378:metabolism; D011379:Prognosis; D015398:Signal Transduction
chemical_list: D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D016023:Integrins; D018832:Molecular Chaperones; D051058:Oncogene Protein v-akt; D020778:Matrix Metalloproteinase 2; C082908:integrin alpha7beta1
keywords: Hsp27; OGX-427.; hepatocellular carcinoma; metastasis; prognosis