title: Hsp27 Acts as a Master Molecular Chaperone and Plays an Essential Role in Hepatocellular Carcinoma Progression.
abstract: OBJECTIVE
  Hsp27, a master molecular chaperone, plays an important role in cancer. However, the specific co-chaperones that partner with Hsp27 and the role of Hsp27 in hepatocellular carcinoma (HCC) are not fully enumerated. The present study focuses on the role of Hsp27 in HCC and explores its potential co-chaperones in HCC development.
  
  
  METHODS
  Gene overexpression or knockdown was used to observe the role of Hsp27 in HCC. Co-immunoprecipitation and mass spectrometry were used to explore apoptosis resistance by regulating multiple co-chaperones of Hsp27. Hsp27 protein-protein interaction (PPI) networks were constructed by the MetaCore software.
  
  
  RESULTS
  Hsp27 was upregulated in HCC tissues, and Hsp27 overexpression significantly facilitated formation of HCC cell colony and invasion in normoxia and tolerance in hypoxia by interacting with HIF-1α. Next, the analysis of microarrays revealed that Hsp27 regulated several cellular signaling pathways, including Wnt, ErbB and TGF-β signaling. Moreover, we characterized the Hsp27 PPI map, which indicated that Hsp27 along with its co-chaperones formed different complexes and exerts transcription regulation activity by activating sp1, c-Myc, p53 and ESR1.
  
  
  CONCLUSIONS
  Hsp27 along with its co-chaperones was related to the development of HCC by regulating multiple signaling pathways, and drugs that target Hsp27 along with its co-chaperones may be a potential therapy for HCC.
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cheng
authors.forename: Zhen
authors.initials: Z
authors.lastname: Lv
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Weng
authors.forename: Sunyi
authors.initials: S
authors.lastname: Ye
authors.forename: Kezhen
authors.initials: K
authors.lastname: Shen
authors.forename: Mansheng
authors.initials: M
authors.lastname: Li
authors.forename: Yunsheng
authors.initials: Y
authors.lastname: Qin
authors.forename: Chen
authors.initials: C
authors.lastname: Hu
authors.forename: Chenxi
authors.initials: C
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.forename: Shusen
authors.initials: S
authors.lastname: Zheng
mesh_terms: D017209:Apoptosis / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000378:metabolism; D018450:Disease Progression; D047628:Estrogen Receptor alpha / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics*; D006360:Heat-Shock Proteins; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D018832:Molecular Chaperones / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D016329:Sp1 Transcription Factor / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D004268:DNA-Binding Proteins; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; C497442:HIF1A protein, human; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C116115:MYCBP protein, human; D018832:Molecular Chaperones; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53