論文

査読有り
2014年4月

ADAM12-cleaved ephrin-A1 contributes to lung metastasis

ONCOGENE
  • K. Ieguchi
  • ,
  • T. Tomita
  • ,
  • T. Omori
  • ,
  • A. Komatsu
  • ,
  • A. Deguchi
  • ,
  • J. Masuda
  • ,
  • S. L. Duffy
  • ,
  • M. G. Coulthard
  • ,
  • A. Boyd
  • ,
  • Y. Maru

33
17
開始ページ
2179
終了ページ
2190
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/onc.2013.180
出版者・発行元
NATURE PUBLISHING GROUP

Eph receptor tyrosine kinases and their ephrin ligands have been implicated in neuronal development and neovascularization. Overexpression of ephrin-A1 has been implicated in tumor progression and poor prognosis. However, the mechanisms are not clear. Here, we report a role of the Eph/ephrin system in a cell adhesion mechanism. Clustered erythropoietin-producing hepatocellular receptor A1 ( EphA1)/ephrin-A1 complexes on the plasma membrane did not undergo endocytosis, and the cell remained adherent to one another. The cell-cell contacts were maintained in an Eph tyrosine kinase activity-independent manner even in the absence of E-cadherin. EphA1 and ephrin-A1 co-localized in pulmonary endothelial cells, and regulated vascular permeability and metastasis in the lungs. We identified ADAM12 ( A disintegrin and metalloproteinase 12) as an EphA1-binding partner by yeast two-hybrid screening and found that ADAM12 enhanced ephrin-A1 cleavage in response to transforming growth factor-b1 in primary tumors. Released soluble ephrin-A1 in the serum deteriorated the EphA1/ephrin-A1-mediated cell adhesion in the lungs in an endocrine manner, causing lung hyperpermeability that facilitated tumor cell entry into the lungs. Depletion of soluble ephrin-A1 by its neutralizing antibody significantly inhibited lung metastasis.

Web of Science ® 被引用回数 : 29

リンク情報
DOI
https://doi.org/10.1038/onc.2013.180
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/23686306
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000334996000004&DestApp=WOS_CPL

エクスポート
BibTeX RIS