Nitric oxide regulates adhesiveness, invasiveness, and migration of anoikis-resistant endothelial cells
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Brazilian Journal of Medical and Biological Research |
Texto Completo: | http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2022000100611 |
Resumo: | Anoikis is a type of apoptosis that occurs in response to the loss of adhesion to the extracellular matrix (ECM). Anoikis resistance is a critical mechanism in cancer and contributes to tumor metastasis. Nitric oxide (NO) is frequently upregulated in the tumor area and is considered an important player in cancer metastasis. The aim of this study was to evaluate the effect of NO on adhesiveness, invasiveness, and migration of anoikis-resistant endothelial cells. Here, we report that anoikis-resistant endothelial cells overexpress endothelial nitric oxide synthase. The inhibition of NO release in anoikis-resistant endothelial cells was able to decrease adhesiveness to fibronectin, laminin, and collagen IV. This was accompanied by an increase in cell invasiveness and migration. Furthermore, anoikis-resistant cell lines displayed a decrease in fibronectin and collagen IV protein expression after L-NAME treatment. These alterations in adhesiveness and invasiveness were the consequence of MMP-2 up-regulation observed after NO release inhibition. The decrease in NO levels was able to down-regulate the activating transcription factor 3 (ATF3) protein expression. ATF3 represses MMP-2 gene expression by antagonizing p53-dependent trans-activation of the MMP-2 promoter. We speculate that the increased release of NO by anoikis-resistant endothelial cells acted as a response to restrict the MMP-2 action, interfering in MMP-2 gene expression via ATF3 regulation. The up-regulation of nitric oxide by anoikis-resistant endothelial cells is an important response to restrict tumorigenic behavior. Without this mechanism, invasiveness and migration potential would be even higher, as shown after L-NAME treatment. |
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Brazilian Journal of Medical and Biological Research |
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Nitric oxide regulates adhesiveness, invasiveness, and migration of anoikis-resistant endothelial cellsAnoikis resistanceNitric oxideEndothelial nitric oxide synthase (eNOS)Metalloproteinase-2 (MMP-2)Endothelial cellAnoikis is a type of apoptosis that occurs in response to the loss of adhesion to the extracellular matrix (ECM). Anoikis resistance is a critical mechanism in cancer and contributes to tumor metastasis. Nitric oxide (NO) is frequently upregulated in the tumor area and is considered an important player in cancer metastasis. The aim of this study was to evaluate the effect of NO on adhesiveness, invasiveness, and migration of anoikis-resistant endothelial cells. Here, we report that anoikis-resistant endothelial cells overexpress endothelial nitric oxide synthase. The inhibition of NO release in anoikis-resistant endothelial cells was able to decrease adhesiveness to fibronectin, laminin, and collagen IV. This was accompanied by an increase in cell invasiveness and migration. Furthermore, anoikis-resistant cell lines displayed a decrease in fibronectin and collagen IV protein expression after L-NAME treatment. These alterations in adhesiveness and invasiveness were the consequence of MMP-2 up-regulation observed after NO release inhibition. The decrease in NO levels was able to down-regulate the activating transcription factor 3 (ATF3) protein expression. ATF3 represses MMP-2 gene expression by antagonizing p53-dependent trans-activation of the MMP-2 promoter. We speculate that the increased release of NO by anoikis-resistant endothelial cells acted as a response to restrict the MMP-2 action, interfering in MMP-2 gene expression via ATF3 regulation. The up-regulation of nitric oxide by anoikis-resistant endothelial cells is an important response to restrict tumorigenic behavior. Without this mechanism, invasiveness and migration potential would be even higher, as shown after L-NAME treatment.Associação Brasileira de Divulgação Científica2022-01-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2022000100611Brazilian Journal of Medical and Biological Research v.55 2022reponame:Brazilian Journal of Medical and Biological Researchinstname:Associação Brasileira de Divulgação Científica (ABDC)instacron:ABDC10.1590/1414-431x2021e11612info:eu-repo/semantics/openAccessMesquita,A.P.S.Matsuoka,M.Lopes,S.A.Pernambuco Filho,P.C.A.Cruz,A.S.Nader,H.B.Lopes,C.C.eng2022-02-01T00:00:00Zoai:scielo:S0100-879X2022000100611Revistahttps://www.bjournal.org/https://old.scielo.br/oai/scielo-oai.phpbjournal@terra.com.br||bjournal@terra.com.br1414-431X0100-879Xopendoar:2022-02-01T00:00Brazilian Journal of Medical and Biological Research - Associação Brasileira de Divulgação Científica (ABDC)false |
dc.title.none.fl_str_mv |
Nitric oxide regulates adhesiveness, invasiveness, and migration of anoikis-resistant endothelial cells |
title |
Nitric oxide regulates adhesiveness, invasiveness, and migration of anoikis-resistant endothelial cells |
spellingShingle |
Nitric oxide regulates adhesiveness, invasiveness, and migration of anoikis-resistant endothelial cells Mesquita,A.P.S. Anoikis resistance Nitric oxide Endothelial nitric oxide synthase (eNOS) Metalloproteinase-2 (MMP-2) Endothelial cell |
title_short |
Nitric oxide regulates adhesiveness, invasiveness, and migration of anoikis-resistant endothelial cells |
title_full |
Nitric oxide regulates adhesiveness, invasiveness, and migration of anoikis-resistant endothelial cells |
title_fullStr |
Nitric oxide regulates adhesiveness, invasiveness, and migration of anoikis-resistant endothelial cells |
title_full_unstemmed |
Nitric oxide regulates adhesiveness, invasiveness, and migration of anoikis-resistant endothelial cells |
title_sort |
Nitric oxide regulates adhesiveness, invasiveness, and migration of anoikis-resistant endothelial cells |
author |
Mesquita,A.P.S. |
author_facet |
Mesquita,A.P.S. Matsuoka,M. Lopes,S.A. Pernambuco Filho,P.C.A. Cruz,A.S. Nader,H.B. Lopes,C.C. |
author_role |
author |
author2 |
Matsuoka,M. Lopes,S.A. Pernambuco Filho,P.C.A. Cruz,A.S. Nader,H.B. Lopes,C.C. |
author2_role |
author author author author author author |
dc.contributor.author.fl_str_mv |
Mesquita,A.P.S. Matsuoka,M. Lopes,S.A. Pernambuco Filho,P.C.A. Cruz,A.S. Nader,H.B. Lopes,C.C. |
dc.subject.por.fl_str_mv |
Anoikis resistance Nitric oxide Endothelial nitric oxide synthase (eNOS) Metalloproteinase-2 (MMP-2) Endothelial cell |
topic |
Anoikis resistance Nitric oxide Endothelial nitric oxide synthase (eNOS) Metalloproteinase-2 (MMP-2) Endothelial cell |
description |
Anoikis is a type of apoptosis that occurs in response to the loss of adhesion to the extracellular matrix (ECM). Anoikis resistance is a critical mechanism in cancer and contributes to tumor metastasis. Nitric oxide (NO) is frequently upregulated in the tumor area and is considered an important player in cancer metastasis. The aim of this study was to evaluate the effect of NO on adhesiveness, invasiveness, and migration of anoikis-resistant endothelial cells. Here, we report that anoikis-resistant endothelial cells overexpress endothelial nitric oxide synthase. The inhibition of NO release in anoikis-resistant endothelial cells was able to decrease adhesiveness to fibronectin, laminin, and collagen IV. This was accompanied by an increase in cell invasiveness and migration. Furthermore, anoikis-resistant cell lines displayed a decrease in fibronectin and collagen IV protein expression after L-NAME treatment. These alterations in adhesiveness and invasiveness were the consequence of MMP-2 up-regulation observed after NO release inhibition. The decrease in NO levels was able to down-regulate the activating transcription factor 3 (ATF3) protein expression. ATF3 represses MMP-2 gene expression by antagonizing p53-dependent trans-activation of the MMP-2 promoter. We speculate that the increased release of NO by anoikis-resistant endothelial cells acted as a response to restrict the MMP-2 action, interfering in MMP-2 gene expression via ATF3 regulation. The up-regulation of nitric oxide by anoikis-resistant endothelial cells is an important response to restrict tumorigenic behavior. Without this mechanism, invasiveness and migration potential would be even higher, as shown after L-NAME treatment. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-01-01 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2022000100611 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2022000100611 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1590/1414-431x2021e11612 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
text/html |
dc.publisher.none.fl_str_mv |
Associação Brasileira de Divulgação Científica |
publisher.none.fl_str_mv |
Associação Brasileira de Divulgação Científica |
dc.source.none.fl_str_mv |
Brazilian Journal of Medical and Biological Research v.55 2022 reponame:Brazilian Journal of Medical and Biological Research instname:Associação Brasileira de Divulgação Científica (ABDC) instacron:ABDC |
instname_str |
Associação Brasileira de Divulgação Científica (ABDC) |
instacron_str |
ABDC |
institution |
ABDC |
reponame_str |
Brazilian Journal of Medical and Biological Research |
collection |
Brazilian Journal of Medical and Biological Research |
repository.name.fl_str_mv |
Brazilian Journal of Medical and Biological Research - Associação Brasileira de Divulgação Científica (ABDC) |
repository.mail.fl_str_mv |
bjournal@terra.com.br||bjournal@terra.com.br |
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1754302948919214080 |