Interaction between HSP60 and beta-catenin promotes metastasis.
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 beta-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 beta-catenin, increases beta-catenin protein levels through the apical domain and enhances its transcriptional activity. Short-interference RNA-mediated repression of beta-catenin reverts metastatic activity caused by HSP60 overexpression. Proteosomal activity is not required for the induction of beta-catenin by HSP60. Coexpression of HSP60 and nuclear beta-catenin predicts a worse prognosis of metastatic head and neck cancer patients. These results implicate a novel role of HSP60 in metastasis.
Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan.
Ya-Ping
YP
Tsai
Muh-Hwa
MH
Yang
Chi-Hung
CH
Huang
Shyue-Yih
SY
Chang
Po-Min
PM
Chen
Chung-Ji
CJ
Liu
Shu-Chun
SC
Teng
Kou-Juey
KJ
Wu
D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000378:metabolism / Q000556:secondary; D002460:Cell Line; D018834:Chaperonin 60 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006258:Head and Neck Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary; D051379:Mice; D009362:Neoplasm Metastasis / Q000473:pathology*; D009368:Neoplasm Transplantation; D011379:Prognosis; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D015533:Transcriptional Activation; D051176:beta Catenin / Q000378:metabolism*
D014408:Biomarkers, Tumor; D018834:Chaperonin 60; D051176:beta Catenin; D046988:Proteasome Endopeptidase Complex