Carcinogenesis Advance Access originally published online on April 15, 2009
Carcinogenesis 2009 30(6):1049-1057; doi:10.1093/carcin/bgp087
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Interaction between HSP60 and β-catenin promotes metastasis
1 Institute of Biochemistry and Molecular Biology
2 Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan
3 Division of Oncology, Department of Medicine
4 Genomic Medicine Center, Taipei Veterans General Hospital, Taipei 112, Taiwan
5 Institute of Biochemistry, National Chung-Hsing University, Taichung 402, Taiwan
6 Department of Otolaryngology, Taipei Veterans General Hospital, Taipei 112, Taiwan
7 Department of Dentistry, Taipei Mackay Memorial Hospital, Taipei 104, Taiwan
8 Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei 100, Taiwan
* To whom correspondence should be addressed. Tel: +011 886 228267328; Fax: +011 886 228264843; Email: kjwu2{at}ym.edu.tw
Heat shock protein 60 (HSP60) plays an essential role in assisting many newly synthesized proteins to reach their native forms. Increased HSP60 expression is observed in different types of human cancers with metastasis (e.g. pancreatic cancer and large bowel carcinoma). However, the role of HSP60 in metastasis remains little known. Aberrant activation of β-catenin plays a key role in tumorigenesis and metastasis. Here, we show that overexpression of HSP60 induces metastatic phenotypes in vitro and in vivo. HSP60 interacts with β-catenin, increases β-catenin protein levels through the apical domain and enhances its transcriptional activity. Short-interference RNA-mediated repression of β-catenin reverts metastatic activity caused by HSP60 overexpression. Proteosomal activity is not required for the induction of β-catenin by HSP60. Coexpression of HSP60 and nuclear β-catenin predicts a worse prognosis of metastatic head and neck cancer patients. These results implicate a novel role of HSP60 in metastasis.
Abbreviations: a.a., amino acid; GST, glutathione-S-transferase; HNSCC, head and neck squamous cell carcinoma; HSP60, heat shock protein 60; IHC, immunohistochemistry; PBS, phosphate-buffered saline; siRNA, short-interference RNA
Received July 1, 2008; revised April 2, 2009; accepted April 7, 2009.