Ephrin-A1 Is Up-Regulated by Hypoxia in Cancer Cells and Promotes Angiogenesis of HUVECs through a Coordinated Cross-Talk with eNOS

Ephrin-A1 Is Up-Regulated by Hypoxia in Cancer Cells and Promotes Angiogenesis of HUVECs through a Coordinated Cross-Talk with eNOS

Hypoxia, ephrin-A1 and endothelial nitric oxide synthase (eNOS) have been proved to play critical roles in tumor angiogenesis. However, how ephrin-A1 is regulated by hypoxia and whether ephrin-A1 cooperates with eNOS in modulation of angiogenesis remain to be addressed in details. Here we demonstrat...

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Main Authors: Song, Yong, Zhao, Xiao-Ping, Song, Kai, Shang, Zheng-Jun
Format: Online
Language:English
Published: Public Library of Science 2013
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3767678/
id pubmed-3767678
recordtype oai_dc
spelling pubmed-37676782013-09-13 Ephrin-A1 Is Up-Regulated by Hypoxia in Cancer Cells and Promotes Angiogenesis of HUVECs through a Coordinated Cross-Talk with eNOS Song, Yong Zhao, Xiao-Ping Song, Kai Shang, Zheng-Jun Research Article Hypoxia, ephrin-A1 and endothelial nitric oxide synthase (eNOS) have been proved to play critical roles in tumor angiogenesis. However, how ephrin-A1 is regulated by hypoxia and whether ephrin-A1 cooperates with eNOS in modulation of angiogenesis remain to be addressed in details. Here we demonstrated that both ephrin-A1 in squamous cell carcinoma cells (SCC-9) and especially soluble ephrin-A1 in the supernatants were up-regulated under hypoxic condition. An increased nitric oxide (NO) production in human umbilical vein endothelial cells (HUVECs) was observed in ephrin-A1-induced angiogenesis which was reversed after co-culture with eNOS specific inhibitor, N-nitro-L-arginine methyl ester hydrochloride (L-NAME). Western blot analysis confirmed that both phosphorylation of AktSer473 and eNOSSer1177 were up-regulated in ephrin-A1-stimulated HUVECs, with the total eNOS expression unchanged. The specific inhibitor of phosphatidylinositol 3-kinase (PI3K), LY294002, significantly down-regulated ephrin-A1-induced expression of phosphorylated AktSer473 as well as phosphorylation of eNOSSer1177. These results revealed a possible novel mechanism whereby ephrin-A1 is regulated in tumor microenvironment and promotes angiogenesis through a coordinated cross-talk with PI3K/Akt-dependent eNOS activation which may relate to normal vascular development and tumor neovascularization. Public Library of Science 2013-09-09 /pmc/articles/PMC3767678/ /pubmed/24040255 http://dx.doi.org/10.1371/journal.pone.0074464 Text en © 2013 Song et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Song, Yong
Zhao, Xiao-Ping
Song, Kai
Shang, Zheng-Jun
spellingShingle Song, Yong
Zhao, Xiao-Ping
Song, Kai
Shang, Zheng-Jun
Ephrin-A1 Is Up-Regulated by Hypoxia in Cancer Cells and Promotes Angiogenesis of HUVECs through a Coordinated Cross-Talk with eNOS
author_facet Song, Yong
Zhao, Xiao-Ping
Song, Kai
Shang, Zheng-Jun
author_sort Song, Yong
title Ephrin-A1 Is Up-Regulated by Hypoxia in Cancer Cells and Promotes Angiogenesis of HUVECs through a Coordinated Cross-Talk with eNOS
title_short Ephrin-A1 Is Up-Regulated by Hypoxia in Cancer Cells and Promotes Angiogenesis of HUVECs through a Coordinated Cross-Talk with eNOS
title_full Ephrin-A1 Is Up-Regulated by Hypoxia in Cancer Cells and Promotes Angiogenesis of HUVECs through a Coordinated Cross-Talk with eNOS
title_fullStr Ephrin-A1 Is Up-Regulated by Hypoxia in Cancer Cells and Promotes Angiogenesis of HUVECs through a Coordinated Cross-Talk with eNOS
title_full_unstemmed Ephrin-A1 Is Up-Regulated by Hypoxia in Cancer Cells and Promotes Angiogenesis of HUVECs through a Coordinated Cross-Talk with eNOS
title_sort ephrin-a1 is up-regulated by hypoxia in cancer cells and promotes angiogenesis of huvecs through a coordinated cross-talk with enos
description Hypoxia, ephrin-A1 and endothelial nitric oxide synthase (eNOS) have been proved to play critical roles in tumor angiogenesis. However, how ephrin-A1 is regulated by hypoxia and whether ephrin-A1 cooperates with eNOS in modulation of angiogenesis remain to be addressed in details. Here we demonstrated that both ephrin-A1 in squamous cell carcinoma cells (SCC-9) and especially soluble ephrin-A1 in the supernatants were up-regulated under hypoxic condition. An increased nitric oxide (NO) production in human umbilical vein endothelial cells (HUVECs) was observed in ephrin-A1-induced angiogenesis which was reversed after co-culture with eNOS specific inhibitor, N-nitro-L-arginine methyl ester hydrochloride (L-NAME). Western blot analysis confirmed that both phosphorylation of AktSer473 and eNOSSer1177 were up-regulated in ephrin-A1-stimulated HUVECs, with the total eNOS expression unchanged. The specific inhibitor of phosphatidylinositol 3-kinase (PI3K), LY294002, significantly down-regulated ephrin-A1-induced expression of phosphorylated AktSer473 as well as phosphorylation of eNOSSer1177. These results revealed a possible novel mechanism whereby ephrin-A1 is regulated in tumor microenvironment and promotes angiogenesis through a coordinated cross-talk with PI3K/Akt-dependent eNOS activation which may relate to normal vascular development and tumor neovascularization.
publisher Public Library of Science
publishDate 2013
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3767678/
_version_ 1612010005939093504

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