Angiotensin Converting Enzyme Regulates Cell Proliferation and Migration

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dc.citation.issue12
dc.citation.volume11
dc.contributor.authorde Alvarenga, Erika Costa
dc.contributor.authorFonseca, Matheus de Castro
dc.contributor.authorCarvalho, Clarissa Coelho
dc.contributor.authorFlorentino, Rodrigo Machado
dc.contributor.authorFranca, Andressa
dc.contributor.authorMatias, Eveline
dc.contributor.authorGuimarães, Paola Bianchi [UNIFESP]
dc.contributor.authorBatista, Carolina [UNIFESP]
dc.contributor.authorFreire, Valder
dc.contributor.authorCarmona, Adriana Karaoglanovic [UNIFESP]
dc.contributor.authorPesquero, João Bosco [UNIFESP]
dc.contributor.authorde Paula, Ana Maria
dc.contributor.authorFoureaux, Giselle
dc.contributor.authorLeite, Maria de Fatima
dc.coverageSan Francisco
dc.date.accessioned2020-07-31T12:47:02Z
dc.date.available2020-07-31T12:47:02Z
dc.date.issued2016
dc.description.abstractBackground The angiotensin-I converting enzyme (ACE) plays a central role in the renin-angiotensin system, acting by converting the hormone angiotensin-I to the active peptide angiotensin-II (Ang-II). More recently, ACE was shown to act as a receptor for Ang-II, and its expression level was demonstrated to be higher in melanoma cells compared to their normal counterparts. However, the function that ACE plays as an Ang-II receptor in melanoma cells has not been defined yet. Aim Therefore, our aim was to examine the role of ACE in tumor cell proliferation and migration. Results We found that upon binding to ACE, Ang-II internalizes with a faster onset compared to the binding of Ang-II to its classical AT1 receptor. We also found that the complex Ang-II/ACE translocates to the nucleus, through a clathrin-mediated process, triggering a transient nuclear Ca2+ signal. In silico studies revealed a possible interaction site between ACE and phospholipase C (PLC), and experimental results in CHO cells, demonstrated that the beta 3 isoform of PLC is the one involved in the Ca2+ signals induced by Ang-II/ACE interaction. Further studies in melanoma cells (TM-5) showed that Ang-II induced cell proliferation through ACE activation, an event that could be inhibited either by ACE inhibitor (Lisinopril) or by the silencing of ACE. In addition, we found that stimulation of ACE by Ang-II caused the melanoma cells to migrate, at least in part due to decreased vinculin expression, a focal adhesion structural protein. Conclusion ACE activation regulates melanoma cell proliferation and migration.en
dc.description.affiliationUniv Fed Minas Gerais, Dept Physiol & Biophys, Belo Horizonte, MG, Brazil
dc.description.affiliationUniv Fed Sao Joao del Rei, Dept Nat Sci, Sao Joao Del Rei, MG, Brazil
dc.description.affiliationUniv Fed Ceara, Dept Phys, Fortaleza, CE, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Biophys, Sao Paulo, SP, Brazil
dc.description.affiliationUniv Fed Minas Gerais, Dept Phys, Belo Horizonte, MG, Brazil
dc.description.affiliationUniv Fed Minas Gerais, Dept Morphol, Belo Horizonte, MG, Brazil
dc.description.affiliationUnifespDepartment of Biophysics, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipINCT Nanocarbono - UFMG (Brazil)
dc.format.extent-
dc.identifierhttp://dx.doi.org/10.1371/journal.pone.0165371
dc.identifier.citationPlos One. San Francisco, v. 11, n. 12, p. -, 2016.
dc.identifier.doi10.1371/journal.pone.0165371
dc.identifier.fileWOS000392842600004.pdf
dc.identifier.issn1932-6203
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/56544
dc.identifier.wosWOS:000392842600004
dc.language.isoeng
dc.publisherPublic Library Science
dc.relation.ispartofPlos One
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleAngiotensin Converting Enzyme Regulates Cell Proliferation and Migrationen
dc.typeinfo:eu-repo/semantics/article
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