Angiotensin Converting Enzyme Regulates Cell Proliferation and Migration

Angiotensin Converting Enzyme Regulates Cell Proliferation and Migration

Author de Alvarenga, Erika Costa Google Scholar
Fonseca, Matheus de Castro Google Scholar
Carvalho, Clarissa Coelho Google Scholar
Florentino, Rodrigo Machado Google Scholar
Franca, Andressa Google Scholar
Matias, Eveline Google Scholar
Guimarães, Paola Bianchi Autor UNIFESP Google Scholar
Batista, Carolina Autor UNIFESP Google Scholar
Freire, Valder Google Scholar
Carmona, Adriana Karaoglanovic Autor UNIFESP Google Scholar
Pesquero, João Bosco Autor UNIFESP Google Scholar
de Paula, Ana Maria Google Scholar
Foureaux, Giselle Google Scholar
Leite, Maria de Fatima Google Scholar
Abstract Background 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.
xmlui.dri2xhtml.METS-1.0.item-coverage San Francisco
Language English
Sponsor Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
INCT Nanocarbono - UFMG (Brazil)
Date 2016
Published in Plos One. San Francisco, v. 11, n. 12, p. -, 2016.
ISSN 1932-6203 (Sherpa/Romeo, impact factor)
Publisher Public Library Science
Extent -
Origin http://dx.doi.org/10.1371/journal.pone.0165371
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000392842600004
URI https://repositorio.unifesp.br/handle/11600/56544

Show full item record




File

Name: WOS000392842600004.pdf
Size: 2.730Mb
Format: PDF
Description:
Open file

This item appears in the following Collection(s)

Search


Browse

Statistics

My Account