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.
Tsai
Ya-Ping
YP
Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan.
Yang
Muh-Hwa
MH
Huang
Chi-Hung
CH
Chang
Shyue-Yih
SY
Chen
Po-Min
PM
Liu
Chung-Ji
CJ
Teng
Shu-Chun
SC
Wu
Kou-Juey
KJ
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