Angiotensin-(1-7) counteracts the transforming effects triggered by angiotensin II in breast cancer cells

dc.contributor.authorCambados, Nadia
dc.contributor.authorWalther, Thomas
dc.contributor.authorNahmod, Karen
dc.contributor.authorTocci, Johanna M.
dc.contributor.authorRubinstein, Natalia
dc.contributor.authorBoehme, Ilka
dc.contributor.authorSimian, Marina
dc.contributor.authorSampayo, Rocio
dc.contributor.authorDel Valle Suberbordes, Melisa
dc.contributor.authorKordon, Edith C.
dc.contributor.authorSchere-Levy, Carolina
dc.contributor.funderDeutsche Forschungsgemeinschaft
dc.contributor.funderMinisterio de Ciencia, Tecnología e Innovación Productiva
dc.contributor.funderNational Cancer Institute
dc.contributor.funderConsejo Nacional de Investigaciones Científicas y Técnicas
dc.contributor.funderAgencia Nacional de Promoción Científica y Tecnológica
dc.description.abstractAngiotensin (Ang) II, the main effector peptide of the renin-angiotensin system, has been implicated in multiple aspects of cancer progression such as proliferation, migration, invasion, angiogenesis and metastasis. Ang-(1-7), is a biologically active heptapeptide, generated predominantly from AngII by the enzymatic activity of angiotensin converting enzyme 2. Previous studies have shown that Ang-(1-7) counterbalances AngII actions in different pathophysiological settings. In this study, we have analysed the impact of Ang( 1-7) on AngII-induced pro-tumorigenic features on normal murine mammary epithelial cells NMuMG and breast cancer cells MDA-MB-231. AngII stimulated the activation of the survival factor AKT in NMuMG cells mainly through the AT1 receptor. This PI3K/AKT pathway activation also promoted epithelial-mesenchymal transition (EMT). Concomitant treatment of NMuMG cells with AngII and Ang-(1-7) completely abolished EMT features induced by AngII. Furthermore, Ang-(1-7) abrogated AngII induced migration and invasion of the MDA-MB-231 cells as well as pro-angiogenic events such as the stimulation of MMP-9 activity and VEGF expression. Together, these results demonstrate for the first time that Ang-(1-7) counteracts tumor aggressive signals stimulated by AngII in breast cancer cells emerging the peptide as a potential therapy to prevent breast cancer progression.en
dc.description.sponsorshipAgencia Nacional de Promoción Científica y Tecnológica (PICT 2011-1638); Consejo Nacional de Investigaciones Científicas y Técnicas (Proyectos de Investigación Plurianuales); Ministerio de Ciencia, Tecnología e Innovación Productiva (Deutscher Akademischer Austauschdienst (DA1203); Deutsche Forschungsgemeinschaft (WA 1441/22-2)en
dc.description.statusPeer reviewed
dc.description.versionPublished Versionen
dc.identifier.citationCambados, N., Walther, T., Nahmod, K., Tocci, J. M., Rubinstein, N., Böhme, I., Simian, M., Sampayo, R., Suberbordes, M. D. V. and Kordon, E. C. (2017) 'Angiotensin-(1-7) counteracts the transforming effects triggered by angiotensin II in breast cancer cells', Oncotarget, 8(51), pp. 88475-88487. doi: 10.18632/oncotarget.19290en
dc.publisherImpact Journalsen
dc.rights© 2017, Cambados et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.subjectAngiotensin iien
dc.subjectBreast cancer cellsen
dc.subjectEpithelial-mesenchymal transitionen
dc.titleAngiotensin-(1-7) counteracts the transforming effects triggered by angiotensin II in breast cancer cellsen
dc.typeArticle (peer-reviewed)en
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Angiotensin-(1-7) counteracts the transforming effects.pdf
3.44 MB
Adobe Portable Document Format
Published Version