ADAM12-cleaved ephrin-A1 contributes to lung metastasis

Ieguchi, K., Tomita, T., Omori, T., Komatsu, A., Deguchi, A., Masuda, J., Duffy, S. L., Coulthard, M. G., Boyd, A. and Maru, Y. (2014) ADAM12-cleaved ephrin-A1 contributes to lung metastasis. Oncogene, 33 17: 2179-2190. doi:10.1038/onc.2013.180

Attached Files (Some files may be inaccessible until you login with your UQ eSpace credentials)
Name Description MIMEType Size Downloads

Author Ieguchi, K.
Tomita, T.
Omori, T.
Komatsu, A.
Deguchi, A.
Masuda, J.
Duffy, S. L.
Coulthard, M. G.
Boyd, A.
Maru, Y.
Title ADAM12-cleaved ephrin-A1 contributes to lung metastasis
Journal name Oncogene   Check publisher's open access policy
ISSN 1476-5594
Publication date 2014-04
Year available 2013
Sub-type Article (original research)
DOI 10.1038/onc.2013.180
Open Access Status
Volume 33
Issue 17
Start page 2179
End page 2190
Total pages 12
Place of publication London United Kingdom
Publisher Nature Publishing Group
Collection year 2015
Language eng
Abstract 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-β1 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.
Keyword Cell adhesion
Tyrosine kinase
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Medicine Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 9 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 14 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Fri, 15 Aug 2014, 18:18:13 EST by System User on behalf of Paediatrics & Child Health - RBWH