2015年2月
UCHL1 provides diagnostic and antimetastatic strategies due to its deubiquitinating effect on HIF-1α
Nature Communications
- 巻
- 6
- 号
- 開始ページ
- 6153
- 終了ページ
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1038/ncomms7153
- 出版者・発行元
- NATURE PUBLISHING GROUP
Hypoxia-inducible factor 1 (HIF-1) plays a role in tumour metastases; however, the genes that activate HIF-1 and subsequently promote metastases have yet to be identified. Here we show that Ubiquitin C-terminal hydrolase-L1 (UCHL1) abrogates the von Hippel-Lindau-mediated ubiquitination of HIF-1α, the regulatory subunit of HIF-1, and consequently promotes metastasis. The aberrant overexpression of UCHL1 facilitates distant tumour metastases in a HIF-1-dependent manner in murine models of pulmonary metastasis. Meanwhile, blockade of the UCHL1-HIF-1 axis suppresses the formation of metastatic tumours. The expression levels of UCHL1 correlate with those of HIF-1α and are strongly associated with the poor prognosis of breast and lung cancer patients. These results indicate that UCHL1 promotes metastases as a deubiquitinating enzyme for HIF-1α, which justifies exploiting it as a prognostic marker and therapeutic target of cancers.
- リンク情報
-
- DOI
- https://doi.org/10.1038/ncomms7153
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/25615526
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000348832600003&DestApp=WOS_CPL
- Scopus
- https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84923076131&origin=inward 本文へのリンクあり
- Scopus Citedby
- https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=84923076131&origin=inward
- ID情報
-
- DOI : 10.1038/ncomms7153
- ISSN : 2041-1723
- eISSN : 2041-1723
- PubMed ID : 25615526
- SCOPUS ID : 84923076131
- Web of Science ID : WOS:000348832600003